Targeting Histone 3 Variants Epigenetic Landscape and Inhibitory
Immune Checkpoints: An Option for Paediatric Brain Tumours Therapy

Sarasa      Meenakshi; Krushna   Ch   Maharana; Lokesh      Nama; Udaya      Kumar Vadla; Sameer      Dhingra; Velayutham      Ravichandiran; Krishna      Murti; Nitesh      Kumar
doi:10.2174/1570159X21666230809110444
Abstract

Despite little progress in survival rates with regular therapies, which do not provide complete care for curing pediatric brain tumors (PBTs), there is an urgent need for novel strategies to overcome the toxic effects of conventional therapies to treat PBTs. The co-inhibitory immune checkpoint molecules, e.g., CTLA-4, PD-1/PD-L1, etc., and epigenetic alterations in histone variants, e.g., H3K27me3 that help in immune evasion at tumor microenvironment have not gained much attention in PBTs treatment. However, key epigenetic mechanistic alterations, such as acetylation, methylation, phosphorylation, sumoylation, poly (ADP)-ribosylation, and ubiquitination in histone protein, are greatly acknowledged. The crucial checkpoints in pediatric brain tumors are cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PDL1), OX-2 membrane glycoprotein (CD200), and indoleamine 2,3-dioxygenase (IDO). This review covers the state of knowledge on the role of multiple co-inhibitory immunological checkpoint proteins and histone epigenetic alterations in different cancers. We further discuss the processes behind these checkpoints, cell signalling, the current scenario of clinical and preclinical research and potential futuristic opportunities for immunotherapies in the treatment of pediatric brain tumors. Conclusively, this article further discusses the possibilities of these interventions to be used for better therapy options.
« Previous Next »
Graphical Abstract

[1]
Dong, H.; Strome, S.E.; Salomao, D.R.; Tamura, H.; Hirano, F.; Flies, D.B.; Roche, P.C.; Lu, J.; Zhu, G.; Tamada, K.; Lennon, V.A.; Celis, E.; Chen, L. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat. Med.,  2002, 8(8), 793-800.
 [http://dx.doi.org/10.1038/nm730] [PMID:  12091876]

[2]
Topalian, S.L.; Drake, C.G.; Pardoll, D.M. Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell,  2015, 27(4), 450-461.
 [http://dx.doi.org/10.1016/j.ccell.2015.03.001] [PMID:  25858804]

[3]
Vignali, D.A.A.; Collison, L.W.; Workman, C.J. How regulatory T cells work. Nat. Rev. Immunol.,  2008, 8(7), 523-532.
 [http://dx.doi.org/10.1038/nri2343] [PMID:  18566595]

[4]
Facciabene, A.; Motz, G.T.; Coukos, G. T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res.,  2012, 72(9), 2162-2171.
 [http://dx.doi.org/10.1158/0008-5472.CAN-11-3687] [PMID:  22549946]

[5]
Baylin, S.B.; Esteller, M.; Rountree, M.R.; Bachman, K.E.; Schuebel, K. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum. Mol. Genet.,  2001, 10(7), 687-692.

[6]
Héninger, E.; Krueger, T.E.; Lang, J.M. Augmenting antitumor immune responses with epigenetic modifying agents. Front. Immunol.,  2015, 6, 49.

[7]
Feinberg, A.P.; Koldobskiy, M.A.; Göndör, A.J.N.R.G. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat. Rev. Genet.,  2016, 17(5), 284-299.
 [http://dx.doi.org/10.1038/nrg.2016.13]

[8]
He, C.; Xu, J.; Zhang, J.; Xie, D.; Ye, H.; Xiao, Z. High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma. Hum. Pathol.,  2012, 43(9), 1425-1435.
 [http://dx.doi.org/10.1016/j.humpath.2011.11.003]

[9]
Hayashi, A.; Yamauchi, N.; Shibahara, J.; Kimura, H.; Morikawa, T.; Ishikawa, S.; Nagae, G.; Nishi, A.; Sakamoto, Y.; Kokudo, N.; Aburatani, H.; Fukayama, M. Concurrent activation of acetylation and tri-methylation of H3K27 in a subset of hepatocellular carcinoma with aggressive behavior. PLoS One,  2014, 9(3), e91330.
 [http://dx.doi.org/10.1371/journal.pone.0091330] [PMID:  24614346]

[10]
Li, D. Zeng, ZJBR Epigenetic regulation of histone H3 in the process of hepatocellular tumorigenesis. Biosci. Rep.,  2019, 39(8), BSR20191815.
 [http://dx.doi.org/10.1042/BSR20191815]

[11]
Berger, S.L.; Kouzarides, T.; Shiekhattar, R.; Shilatifard, A. An operational definition of epigenetics. Genes Dev.,  2009, 23(7), 781-783.
 [http://dx.doi.org/10.1101/gad.1787609] [PMID:  19339683]

[12]
Xu, G.L.; Bestor, T.H.; Bourc’his, D.; Hsieh, C.L.; Tommerup, N.; Bugge, M.; Hulten, M.; Qu, X.; Russo, J.J.; Viegas-Péquignot, E. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature,  1999, 402(6758), 187-191.
 [http://dx.doi.org/10.1038/46052] [PMID:  10647011]

[13]
Portela, A.; Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol.,  2010, 28(10), 1057-1068.
 [http://dx.doi.org/10.1038/nbt.1685] [PMID:  20944598]

[14]
Baylin, S.B.; Ohm, J.E. Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? Nat. Rev. Cancer,  2006, 6(2), 107-116.
 [http://dx.doi.org/10.1038/nrc1799] [PMID:  16491070]

[15]
Suzuki, M.M.; Bird, A. DNA methylation landscapes: provocative insights from epigenomics. Nat. Rev. Genet.,  2008, 9(6), 465-476.
 [http://dx.doi.org/10.1038/nrg2341] [PMID:  18463664]

[16]
Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev.,  2002, 16(1), 6-21.
 [http://dx.doi.org/10.1101/gad.947102] [PMID:  11782440]

[17]
Esteller, M. Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum. Mol. Genet.,  2007, 16(R1), R50-R59.
 [http://dx.doi.org/10.1093/hmg/ddm018] [PMID:  17613547]

[18]
Lopez-Serra, L.; Esteller, M. Proteins that bind methylated DNA and human cancer: reading the wrong words. Br. J. Cancer,  2008, 98(12), 1881-1885.
 [http://dx.doi.org/10.1038/sj.bjc.6604374] [PMID:  18542062]

[19]
Sharma, S.V.; Lee, D.Y.; Li, B.; Quinlan, M.P.; Takahashi, F.; Maheswaran, S.; McDermott, U.; Azizian, N.; Zou, L.; Fischbach, M.A.; Wong, K.K.; Brandstetter, K.; Wittner, B.; Ramaswamy, S.; Classon, M.; Settleman, J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell,  2010, 141(1), 69-80.
 [http://dx.doi.org/10.1016/j.cell.2010.02.027] [PMID:  20371346]

[20]
Kelly, T.K.; De Carvalho, D.D.; Jones, P.A. Epigenetic modifications as therapeutic targets. Nat. Biotechnol.,  2010, 28(10), 1069-1078.
 [http://dx.doi.org/10.1038/nbt.1678] [PMID:  20944599]

[21]
Stupp, R.; Hegi, M.E.; Mason, W.P.; van den Bent, M.J.; Taphoorn, M.J.B.; Janzer, R.C.; Ludwin, S.K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; Brandes, A.A.; Gijtenbeek, J.; Marosi, C.; Vecht, C.J.; Mokhtari, K.; Wesseling, P.; Villa, S.; Eisenhauer, E.; Gorlia, T.; Weller, M.; Lacombe, D.; Cairncross, J.G.; Mirimanoff, R.O. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol.,  2009, 10(5), 459-466.
 [http://dx.doi.org/10.1016/S1470-2045(09)70025-7] [PMID:  19269895]

[22]
Broniscer, A.; Chintagumpala, M.; Fouladi, M.; Krasin, M.J.; Kocak, M.; Bowers, D.C.; Iacono, L.C.; Merchant, T.E.; Stewart, C.F.; Houghton, P.J.; Kun, L.E.; Ledet, D.; Gajjar, A. Temozolomide after radiotherapy for newly diagnosed high-grade glioma and unfavorable low-grade glioma in children. J. Neurooncol.,  2006, 76(3), 313-319.
 [http://dx.doi.org/10.1007/s11060-005-7409-5] [PMID:  16200343]

[23]
Cohen, K.J.; Pollack, I.F.; Zhou, T.; Buxton, A.; Holmes, E.J.; Burger, P.C.; Brat, D.J.; Rosenblum, M.K.; Hamilton, R.L.; Lavey, R.S.; Heideman, R.L. Temozolomide in the treatment of high-grade gliomas in children: a report from the Children’s Oncology Group. Neuro-oncol.,  2011, 13(3), 317-323.
 [http://dx.doi.org/10.1093/neuonc/noq191] [PMID:  21339192]

[24]
Lashford, L.S.; Thiesse, P.; Jouvet, A.; Jaspan, T.; Couanet, D.; Griffiths, P.D.; Doz, F.; Ironside, J.; Robson, K.; Hobson, R.; Dugan, M.; Pearson, A.D.J.; Vassal, G.; Frappaz, D. Temozolomide in malignant gliomas of childhood: A united kingdom children’s cancer study group and french society for pediatric oncology intergroup study. J. Clin. Oncol.,  2002, 20(24), 4684-4691.
 [http://dx.doi.org/10.1200/JCO.2002.08.141] [PMID:  12488414]

[25]
Ruggiero, A.; Cefalo, G.; Garré, M.L.; Massimino, M.; Colosimo, C.; Attinà, G.; Lazzareschi, I.; Maurizi, P.; Ridola, V.; Mazzarella, G.; Caldarelli, M.; Rocco, C.D.; Madon, E.; Abate, M.E.; Clerico, A.; Sandri, A.; Riccardi, R. Phase II trial of temozolomide in children with recurrent high-grade glioma. J. Neurooncol.,  2006, 77(1), 89-94.
 [http://dx.doi.org/10.1007/s11060-005-9011-2] [PMID:  16292488]

[26]
Korshunov, A.; Ryzhova, M.; Hovestadt, V.; Bender, S.; Sturm, D.; Capper, D.; Meyer, J.; Schrimpf, D.; Kool, M.; Northcott, P.A.; Zheludkova, O.; Milde, T.; Witt, O.; Kulozik, A.E.; Reifenberger, G.; Jabado, N.; Perry, A.; Lichter, P.; von Deimling, A.; Pfister, S.M.; Jones, D.T.W. Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol.,  2015, 129(5), 669-678.
 [http://dx.doi.org/10.1007/s00401-015-1405-4] [PMID:  25752754]

[27]
Chassot, A.; Canale, S.; Varlet, P.; Puget, S.; Roujeau, T.; Negretti, L.; Dhermain, F.; Rialland, X.; Raquin, M.A.; Grill, J.; Dufour, C. Radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. J. Neurooncol.,  2012, 106(2), 399-407.
 [http://dx.doi.org/10.1007/s11060-011-0681-7] [PMID:  21858607]

[28]
Cohen, K.J.; Heideman, R.L.; Zhou, T.; Holmes, E.J.; Lavey, R.S.; Bouffet, E.; Pollack, I.F. Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children’s Oncology Group. Neuro-oncol.,  2011, 13(4), 410-416.
 [http://dx.doi.org/10.1093/neuonc/noq205] [PMID:  21345842]

[29]
Hargrave, D.; Bartels, U.; Bouffet, E. Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol.,  2006, 7(3), 241-248.
 [http://dx.doi.org/10.1016/S1470-2045(06)70615-5] [PMID:  16510333]

[30]
Rizzo, D.; Scalzone, M.; Ruggiero, A.; Maurizi, P.; Attinà, G.; Mastrangelo, S.; Lazzareschi, I.; Ridola, V.; Colosimo, C.; Caldarelli, M.; Balducci, M.; Riccardi, R. Temozolomide in the treatment of newly diagnosed diffuse brainstem glioma in children: a broken promise? J. Chemother.,  2015, 27(2), 106-110.
 [http://dx.doi.org/10.1179/1973947814Y.0000000228] [PMID:  25466729]

[31]
Grasso, C.S.; Tang, Y.; Truffaux, N.; Berlow, N.E.; Liu, L.; Debily, M.A.; Quist, M.J.; Davis, L.E.; Huang, E.C.; Woo, P.J.; Ponnuswami, A.; Chen, S.; Johung, T.B.; Sun, W.; Kogiso, M.; Du, Y.; Qi, L.; Huang, Y.; Hütt-Cabezas, M.; Warren, K.E.; Le Dret, L.; Meltzer, P.S.; Mao, H.; Quezado, M.; van Vuurden, D.G.; Abraham, J.; Fouladi, M.; Svalina, M.N.; Wang, N.; Hawkins, C.; Nazarian, J.; Alonso, M.M.; Raabe, E.H.; Hulleman, E.; Spellman, P.T.; Li, X.N.; Keller, C.; Pal, R.; Grill, J.; Monje, M. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat. Med.,  2015, 21(6), 555-559.
 [http://dx.doi.org/10.1038/nm.3855] [PMID:  25939062]

[32]
Hashizume, R.; Andor, N.; Ihara, Y.; Lerner, R.; Gan, H.; Chen, X.; Fang, D.; Huang, X.; Tom, M.W.; Ngo, V.; Solomon, D.; Mueller, S.; Paris, P.L.; Zhang, Z.; Petritsch, C.; Gupta, N.; Waldman, T.A.; James, C.D. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat. Med.,  2014, 20(12), 1394-1396.
 [http://dx.doi.org/10.1038/nm.3716] [PMID:  25401693]

[33]
Keir, M.E.; Liang, S.C.; Guleria, I.; Latchman, Y.E.; Qipo, A.; Albacker, L.A.; Koulmanda, M.; Freeman, G.J.; Sayegh, M.H.; Sharpe, A.H. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J. Exp. Med.,  2006, 203(4), 883-895.
 [http://dx.doi.org/10.1084/jem.20051776] [PMID:  16606670]

[34]
Ohigashi, Y.; Sho, M.; Yamada, Y.; Tsurui, Y.; Hamada, K.; Ikeda, N.; Mizuno, T.; Yoriki, R.; Kashizuka, H.; Yane, K.; Tsushima, F.; Otsuki, N.; Yagita, H.; Azuma, M.; Nakajima, Y. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin. Cancer Res.,  2005, 11(8), 2947-2953.
 [http://dx.doi.org/10.1158/1078-0432.CCR-04-1469] [PMID:  15837746]

[35]
Patel, S.P.; Kurzrock, R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol. Cancer Ther.,  2015, 14(4), 847-856.
 [http://dx.doi.org/10.1158/1535-7163.MCT-14-0983] [PMID:  25695955]

[36]
Lussier, D.M.; O’Neill, L.; Nieves, L.M.; McAfee, M.S.; Holechek, S.A.; Collins, A.W.; Dickman, P.; Jacobsen, J.; Hingorani, P.; Blattman, J.N. Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1 interactions. J. Immunother.,  2015, 38(3), 96-106.
 [http://dx.doi.org/10.1097/CJI.0000000000000065] [PMID:  25751499]

[37]
Pham, C.D.; Flores, C.; Yang, C.; Pinheiro, E.M.; Yearley, J.H.; Sayour, E.J.; Pei, Y.; Moore, C.; McLendon, R.E.; Huang, J.; Sampson, J.H.; Wechsler-Reya, R.; Mitchell, D.A. Differential immune microenvironments and response to immune checkpoint blockade among molecular subtypes of murine medulloblastoma. Clin. Cancer Res.,  2016, 22(3), 582-595.
 [http://dx.doi.org/10.1158/1078-0432.CCR-15-0713] [PMID:  26405194]

[38]
Aoki, T.; Hino, M.; Koh, K.; Kyushiki, M.; Kishimoto, H.; Arakawa, Y.; Hanada, R.; Kawashima, H.; Kurihara, J.; Shimojo, N.; Motohashi, S. Low frequency of programmed death ligand 1 expression in pediatric cancers. Pediatr. Blood Cancer,  2016, 63(8), 1461-1464.
 [http://dx.doi.org/10.1002/pbc.26018] [PMID:  27135656]

[39]
Chowdhury, F.; Dunn, S.; Mitchell, S.; Mellows, T.; Ashton-Key, M.; Gray, J.C. PD-L1 and CD8 + PD1 + lymphocytes exist as targets in the pediatric tumor microenvironment for immunomodulatory therapy. OncoImmunology,  2015, 4(10), e1029701.
 [http://dx.doi.org/10.1080/2162402X.2015.1029701]

[40]
Kim, C.; Kim, E.K.; Jung, H.; Chon, H.J.; Han, J.W.; Shin, K.H.; Hu, H.; Kim, K.S.; Choi, Y.D.; Kim, S.; Lee, Y.H.; Suh, J.S.; Ahn, J.B.; Chung, H.C.; Noh, S.H.; Rha, S.Y.; Kim, S.H.; Kim, H.S. Prognostic implications of PD-L1 expression in patients with soft tissue sarcoma. BMC Cancer,  2016, 16(1), 434.
 [http://dx.doi.org/10.1186/s12885-016-2451-6] [PMID:  27393385]

[41]
Majzner, R.G.; Simon, J.S.; Grosso, J.F.; Martinez, D.; Pawel, B.; Santi-Vincini, M.; Merchant, M.S.; Sorensen, P.; Mackall, C.L.; Maris, J.M. Abstract 249: Assessment of PD-L1 expression and
	tumor-associated lymphocytes in pediatric cancer tissues. Cancer
	Res., 2015, 75(15_Supplement)(Suppl.), 249. 
 [http://dx.doi.org/10.1158/1538-7445.AM2015-249]

[42]
Routh, J.C.; Ashley, R.A.; Sebo, T.J.; Lohse, C.M.; Husmann, D.A.; Kramer, S.A.; Kwon, E.D. B7-H1 expression in Wilms tumor: correlation with tumor biology and disease recurrence. J. Urol.,  2008, 179(5), 1954-1960.
 [http://dx.doi.org/10.1016/j.juro.2008.01.056] [PMID:  18355839]

[43]
Bhaijee, F.; Anders, R.A. PD-L1 Expression as a Predictive Biomarker. JAMA Oncol.,  2016, 2(1), 54-55.
 [http://dx.doi.org/10.1001/jamaoncol.2015.3782] [PMID:  26561922]

[44]
Boes, M.; Meyer-Wentrup, F. TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells. Cancer Lett.,  2015, 361(1), 49-56.
 [http://dx.doi.org/10.1016/j.canlet.2015.02.027] [PMID:  25697485]

[45]
Usui, Y.; Okunuki, Y.; Hattori, T.; Takeuchi, M.; Kezuka, T.; Goto, H.; Usui, M. Expression of costimulatory molecules on human retinoblastoma cells Y-79: functional expression of CD40 and B7H1. Invest. Ophthalmol. Vis. Sci.,  2006, 47(10), 4607-4613.
 [http://dx.doi.org/10.1167/iovs.06-0181] [PMID:  17003458]

[46]
Mao, Y.; Eissler, N.; Blanc, K.L.; Johnsen, J.I.; Kogner, P.; Kiessling, R. Targeting suppressive myeloid cells potentiates checkpoint inhibitors to control spontaneous neuroblastoma. Clin. Cancer Res.,  2016, 22(15), 3849-3859.
 [http://dx.doi.org/10.1158/1078-0432.CCR-15-1912] [PMID:  26957560]

[47]
Brahmer, J.; Reckamp, K.L.; Baas, P.; Crinò, L.; Eberhardt, W.E.E.; Poddubskaya, E.; Antonia, S.; Pluzanski, A.; Vokes, E.E.; Holgado, E.; Waterhouse, D.; Ready, N.; Gainor, J.; Arén Frontera, O.; Havel, L.; Steins, M.; Garassino, M.C.; Aerts, J.G.; Domine, M.; Paz-Ares, L.; Reck, M.; Baudelet, C.; Harbison, C.T.; Lestini, B.; Spigel, D.R. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N. Engl. J. Med.,  2015, 373(2), 123-135.
 [http://dx.doi.org/10.1056/NEJMoa1504627] [PMID:  26028407]

[48]
Motzer, R.J.; Escudier, B.; McDermott, D.F.; George, S.; Hammers, H.J.; Srinivas, S.; Tykodi, S.S.; Sosman, J.A.; Procopio, G.; Plimack, E.R.; Castellano, D.; Choueiri, T.K.; Gurney, H.; Donskov, F.; Bono, P.; Wagstaff, J.; Gauler, T.C.; Ueda, T.; Tomita, Y.; Schutz, F.A.; Kollmannsberger, C.; Larkin, J.; Ravaud, A.; Simon, J.S.; Xu, L.A.; Waxman, I.M.; Sharma, P. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med.,  2015, 373(19), 1803-1813.
 [http://dx.doi.org/10.1056/NEJMoa1510665] [PMID:  26406148]

[49]
Robert, C.; Schachter, J.; Long, G.V.; Arance, A.; Grob, J.J.; Mortier, L.; Daud, A.; Carlino, M.S.; McNeil, C.; Lotem, M.; Larkin, J.; Lorigan, P.; Neyns, B.; Blank, C.U.; Hamid, O.; Mateus, C.; Shapira-Frommer, R.; Kosh, M.; Zhou, H.; Ibrahim, N.; Ebbinghaus, S.; Ribas, A. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med.,  2015, 372(26), 2521-2532.
 [http://dx.doi.org/10.1056/NEJMoa1503093] [PMID:  25891173]

[50]
Rosenberg, J.E.; Hoffman-Censits, J.; Powles, T.; van der Heijden, M.S.; Balar, A.V.; Necchi, A.; Dawson, N.; O’Donnell, P.H.; Balmanoukian, A.; Loriot, Y.; Srinivas, S.; Retz, M.M.; Grivas, P.; Joseph, R.W.; Galsky, M.D.; Fleming, M.T.; Petrylak, D.P.; Perez-Gracia, J.L.; Burris, H.A.; Castellano, D.; Canil, C.; Bellmunt, J.; Bajorin, D.; Nickles, D.; Bourgon, R.; Frampton, G.M.; Cui, N.; Mariathasan, S.; Abidoye, O.; Fine, G.D.; Dreicer, R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet,  2016, 387(10031), 1909-1920.
 [http://dx.doi.org/10.1016/S0140-6736(16)00561-4] [PMID:  26952546]

[51]
Valsecchi, M.E. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med.,  2015, 373(13), 1270-1271.
 [http://dx.doi.org/10.1056/NEJMc1509660] [PMID:  26398077]

[52]
Carbognin, L.; Pilotto, S.; Milella, M.; Vaccaro, V.; Brunelli, M.; Caliò, A.; Cuppone, F.; Sperduti, I.; Giannarelli, D.; Chilosi, M.; Bronte, V.; Scarpa, A.; Bria, E.; Tortora, G. Differential activity of nivolumab, pembrolizumab and MPDL3280A according to the tumor expression of programmed death-ligand-1 (PD-L1): Sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PLoS One,  2015, 10(6), e0130142.
 [http://dx.doi.org/10.1371/journal.pone.0130142] [PMID:  26086854]

[53]
Bouffet, E.; Larouche, V.; Campbell, B.B.; Merico, D.; de Borja, R.; Aronson, M.; Durno, C.; Krueger, J.; Cabric, V.; Ramaswamy, V.; Zhukova, N.; Mason, G.; Farah, R.; Afzal, S.; Yalon, M.; Rechavi, G.; Magimairajan, V.; Walsh, M.F.; Constantini, S.; Dvir, R.; Elhasid, R.; Reddy, A.; Osborn, M.; Sullivan, M.; Hansford, J.; Dodgshun, A.; Klauber-Demore, N.; Peterson, L.; Patel, S.; Lindhorst, S.; Atkinson, J.; Cohen, Z.; Laframboise, R.; Dirks, P.; Taylor, M.; Malkin, D.; Albrecht, S.; Dudley, R.W.R.; Jabado, N.; Hawkins, C.E.; Shlien, A.; Tabori, U. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J. Clin. Oncol.,  2016, 34(19), 2206-2211.
 [http://dx.doi.org/10.1200/JCO.2016.66.6552] [PMID:  27001570]

[54]
Alegre, M.L.; Noel, P.J.; Eisfelder, B.J.; Chuang, E.; Clark, M.R.; Reiner, S.L.; Thompson, C.B. Regulation of surface and intracellular expression of CTLA4 on mouse T cells. J. Immunol.,  1996, 157(11), 4762-4770.
 [http://dx.doi.org/10.4049/jimmunol.157.11.4762] [PMID:  8943377]

[55]
Linsley, P.S.; Bradshaw, J.; Greene, J.; Peach, R.; Bennett, K.L.; Mittler, R.S. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity,  1996, 4(6), 535-543.
 [http://dx.doi.org/10.1016/S1074-7613(00)80480-X] [PMID:  8673700]

[56]
Noel, P.J.; Boise, L.H.; Green, J.M.; Thompson, C.B. CD28 costimulation prevents cell death during primary T cell activation. J. Immunol.,  1996, 157(2), 636-642.
 [http://dx.doi.org/10.4049/jimmunol.157.2.636] [PMID:  8752911]

[57]
Wing, K.; Onishi, Y.; Prieto-Martin, P.; Yamaguchi, T.; Miyara, M.; Fehervari, Z.; Nomura, T.; Sakaguchi, S. CTLA-4 control over Foxp3+ regulatory T cell function. Science,  2008, 322(5899), 271-275.
 [http://dx.doi.org/10.1126/science.1160062] [PMID:  18845758]

[58]
Selby, M.J.; Engelhardt, J.J.; Quigley, M.; Henning, K.A.; Chen, T.; Srinivasan, M.; Korman, A.J. Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol. Res.,  2013, 1(1), 32-42.
 [http://dx.doi.org/10.1158/2326-6066.CIR-13-0013] [PMID:  24777248]

[59]
Peggs, K.S.; Quezada, S.A.; Chambers, C.A.; Korman, A.J.; Allison, J.P. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J. Exp. Med.,  2009, 206(8), 1717-1725.
 [http://dx.doi.org/10.1084/jem.20082492] [PMID:  19581407]

[60]
Sun, T.; Zhou, Y.; Yang, M.; Hu, Z.; Tan, W.; Han, X.; Shi, Y.; Yao, J.; Guo, Y.; Yu, D.; Tian, T.; Zhou, X.; Shen, H.; Lin, D. Functional genetic variations in cytotoxic T-lymphocyte antigen 4 and susceptibility to multiple types of cancer. Cancer Res.,  2008, 68(17), 7025-7034.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-0806] [PMID:  18757416]

[61]
Yu, F.; Miao, J. Significant association between cytotoxic T lymphocyte antigen 4 +49G>A polymorphism and risk of malignant bone tumors. Tumour Biol.,  2013, 34(6), 3371-3375.

[62]
Hurwitz, A.A.; Yu, T.F.Y.; Leach, D.R.; Allison, J.P. CTLA-4 blockade synergizes with tumor-derived granulocyte- macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc. Natl. Acad. Sci. USA,  1998, 95(17), 10067-10071.
 [http://dx.doi.org/10.1073/pnas.95.17.10067] [PMID:  9707601]

[63]
Kwon, E.D.; Hurwitz, A.A.; Foster, B.A.; Madias, C.; Feldhaus, A.L.; Greenberg, N.M.; Burg, M.B.; Allison, J.P. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc. Natl. Acad. Sci. USA,  1997, 94(15), 8099-8103.
 [http://dx.doi.org/10.1073/pnas.94.15.8099] [PMID:  9223321]

[64]
Leach, D.R.; Krummel, M.F.; Allison, J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science,  1996, 271(5256), 1734-1736.
 [http://dx.doi.org/10.1126/science.271.5256.1734] [PMID:  8596936]

[65]
Contardi, E.; Palmisano, G.L.; Tazzari, P.L.; Martelli, A.M.; Falà, F.; Fabbi, M.; Kato, T.; Lucarelli, E.; Donati, D.; Polito, L.; Bolognesi, A.; Ricci, F.; Salvi, S.; Gargaglione, V.; Mantero, S.; Alberghini, M.; Ferrara, G.B.; Pistillo, M.P. CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int. J. Cancer,  2005, 117(4), 538-550.
 [http://dx.doi.org/10.1002/ijc.21155] [PMID:  15912538]

[66]
Merchant, M.S.; Wright, M.; Baird, K.; Wexler, L.H.; Rodriguez-Galindo, C.; Bernstein, D.; Delbrook, C.; Lodish, M.; Bishop, R.; Wolchok, J.D.; Streicher, H.; Mackall, C.L.; Phase, I. Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors. Clin. Cancer Res.,  2016, 22(6), 1364-1370.
 [http://dx.doi.org/10.1158/1078-0432.CCR-15-0491] [PMID:  26534966]

[67]
Eggermont, A.M.M.; Chiarion-Sileni, V.; Grob, J.J.; Dummer, R.; Wolchok, J.D.; Schmidt, H.; Hamid, O.; Robert, C.; Ascierto, P.A.; Richards, J.M.; Lebbé, C.; Ferraresi, V.; Smylie, M.; Weber, J.S.; Maio, M.; Konto, C.; Hoos, A.; de Pril, V.; Gurunath, R.K.; de Schaetzen, G.; Suciu, S.; Testori, A. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol.,  2015, 16(5), 522-530.
 [http://dx.doi.org/10.1016/S1470-2045(15)70122-1] [PMID:  25840693]

[68]
Ribas, A.; Kefford, R.; Marshall, M.A.; Punt, C.J.A.; Haanen, J.B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K.L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G.A.; Dreno, B.; Nathan, P.D.; Mackiewicz, J.; Kirkwood, J.M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J. Clin. Oncol.,  2013, 31(5), 616-622.
 [http://dx.doi.org/10.1200/JCO.2012.44.6112] [PMID:  23295794]

[69]
Wright, G.J.; Jones, M.; Puklavec, M.J.; Brown, M.H.; Barclay, A.N. The unusual distribution of the neuronal/lymphoid cell surface CD200 (OX2) glycoprotein is conserved in humans. Immunology,  2001, 102(2), 173-179.
 [http://dx.doi.org/10.1046/j.1365-2567.2001.01163.x] [PMID:  11260322]

[70]
Hoek, R.M.; Ruuls, S.R.; Murphy, C.A.; Wright, G.J.; Goddard, R.; Zurawski, S.M.; Blom, B.; Homola, M.E.; Streit, W.J.; Brown, M.H.; Barclay, A.N.; Sedgwick, J.D. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science,  2000, 290(5497), 1768-1771.
 [http://dx.doi.org/10.1126/science.290.5497.1768] [PMID:  11099416]

[71]
Jenmalm, M.C.; Cherwinski, H.; Bowman, E.P.; Phillips, J.H.; Sedgwick, J.D. Regulation of myeloid cell function through the CD200 receptor. J. Immunol.,  2006, 176(1), 191-199.
 [http://dx.doi.org/10.4049/jimmunol.176.1.191] [PMID:  16365410]

[72]
Gorczynski, R.M.; Lee, L.; Boudakov, I. Augmented Induction of CD4+CD25+ Treg using monoclonal antibodies to CD200R. Transplantation,  2005, 79(9), 1180-1183.
 [http://dx.doi.org/10.1097/01.TP.0000152118.51622.F9] [PMID:  15880066]

[73]
McWhirter, J.R.; Kretz-Rommel, A.; Saven, A.; Maruyama, T.; Potter, K.N.; Mockridge, C.I.; Ravey, E.P.; Qin, F.; Bowdish, K.S. Antibodies selected from combinatorial libraries block a tumor antigen that plays a key role in immunomodulation. Proc. Natl. Acad. Sci. USA,  2006, 103(4), 1041-1046.
 [http://dx.doi.org/10.1073/pnas.0510081103] [PMID:  16418292]

[74]
Kretz-Rommel, A.; Qin, F.; Dakappagari, N.; Ravey, E.P.; McWhirter, J.; Oltean, D.; Frederickson, S.; Maruyama, T.; Wild, M.A.; Nolan, M.J.; Wu, D.; Springhorn, J.; Bowdish, K.S. CD200 expression on tumor cells suppresses antitumor immunity: new approaches to cancer immunotherapy. J. Immunol.,  2007, 178(9), 5595-5605.
 [http://dx.doi.org/10.4049/jimmunol.178.9.5595] [PMID:  17442942]

[75]
Coles, S.J.; Hills, R.K.; Wang, E.C.Y.; Burnett, A.K.; Man, S.; Darley, R.L.; Tonks, A. Increased CD200 expression in acute myeloid leukemia is linked with an increased frequency of FoxP3+ regulatory T cells. Leukemia,  2012, 26(9), 2146-2148.
 [http://dx.doi.org/10.1038/leu.2012.75] [PMID:  22430636]

[76]
Damiani, D.; Tiribelli, M.; Raspadori, D.; Sirianni, S.; Meneghel, A.; Cavalllin, M.; Michelutti, A.; Toffoletti, E.; Geromin, A.; Simeone, E.; Bocchia, M.; Fanin, R. Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors. Oncotarget,  2015, 6(30), 30212-30221.
 [http://dx.doi.org/10.18632/oncotarget.4901] [PMID:  26338961]

[77]
Moertel, C.L.; Xia, J.; LaRue, R.; Waldron, N.N.; Andersen, B.M.; Prins, R.M.; Okada, H.; Donson, A.M.; Foreman, N.K.; Hunt, M.A.; Pennell, C.A.; Olin, M.R. CD200 in CNS tumor-induced immunosuppression: the role for CD200 pathway blockade in targeted immunotherapy. J. Immunother. Cancer,  2014, 2(1), 46.
 [http://dx.doi.org/10.1186/s40425-014-0046-9] [PMID:  25598973]

[78]
Siva, A.; Xin, H.; Qin, F.; Oltean, D.; Bowdish, K.S.; Kretz-Rommel, A. Immune modulation by melanoma and ovarian tumor cells through expression of the immunosuppressive molecule CD200. Cancer Immunol. Immunother.,  2008, 57(7), 987-996.
 [http://dx.doi.org/10.1007/s00262-007-0429-6] [PMID:  18060403]

[79]
Alexander, W. American society of hematology, 52nd annual meeting and exposition. PT,  2011, 36(2), 100-103.

[80]
Dai, X.; Zhu, B.T. Indoleamine 2,3-dioxygenase tissue distribution and cellular localization in mice: implications for its biological functions. J. Histochem. Cytochem.,  2010, 58(1), 17-28.
 [http://dx.doi.org/10.1369/jhc.2009.953604] [PMID:  19741271]

[81]
Guillemin, G.J.; Smythe, G.; Takikawa, O.; Brew, B.J. Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons. Glia,  2005, 49(1), 15-23.
 [http://dx.doi.org/10.1002/glia.20090] [PMID:  15390107]

[82]
Takikawa, O. Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated l-tryptophan metabolism. Biochem. Biophys. Res. Commun.,  2005, 338(1), 12-19.
 [http://dx.doi.org/10.1016/j.bbrc.2005.09.032] [PMID:  16176799]

[83]
Frumento, G.; Rotondo, R.; Tonetti, M.; Damonte, G.; Benatti, U.; Ferrara, G.B. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J. Exp. Med.,  2002, 196(4), 459-468.
 [http://dx.doi.org/10.1084/jem.20020121] [PMID:  12186838]

[84]
Werner-Felmayer, G.; Werner, E.R.; Fuchs, D.; Hausen, A.; Reibnegger, G.; Wachter, H. Characteristics of interferon induced tryptophan metabolism in human cells in vitro. Biochim. Biophys. Acta Mol. Cell Res.,  1989, 1012(2), 140-147.
 [http://dx.doi.org/10.1016/0167-4889(89)90087-6] [PMID:  2500976]

[85]
Wolf, A.; Wolf, D.; Rumpold, H.; Moschen, A.R.; Kaser, A.; Obrist, P.; Fuchs, D.; Brandacher, G.; Winkler, C.; Geboes, K.; Rutgeerts, P.; Tilg, H. Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease. Clin. Immunol.,  2004, 113(1), 47-55.
 [http://dx.doi.org/10.1016/j.clim.2004.05.004] [PMID:  15380529]

[86]
Munn, D.H.; Zhou, M.; Attwood, J.T.; Bondarev, I.; Conway, S.J.; Marshall, B.; Brown, C.; Mellor, A.L. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science,  1998, 281(5380), 1191-1193.
 [http://dx.doi.org/10.1126/science.281.5380.1191] [PMID:  9712583]

[87]
Uyttenhove, C.; Pilotte, L.; Théate, I.; Stroobant, V.; Colau, D.; Parmentier, N.; Boon, T.; Van den Eynde, B.J. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med.,  2003, 9(10), 1269-1274.
 [http://dx.doi.org/10.1038/nm934] [PMID:  14502282]

[88]
Soliman, H.H.; Minton, S.E.; Han, H.S.; Ismail-Khan, R.; Neuger, A.; Khambati, F.; Noyes, D.; Lush, R.; Chiappori, A.A.; Roberts, J.D.; Link, C.; Vahanian, N.N.; Mautino, M.; Streicher, H.; Sullivan, D.M.; Antonia, S.J. A phase I study of indoximod in patients with advanced malignancies. Oncotarget,  2016, 7(16), 22928-22938.
 [http://dx.doi.org/10.18632/oncotarget.8216] [PMID:  27008709]

[89]
Urakawa, H.; Nishida, Y.; Nakashima, H.; Shimoyama, Y.; Nakamura, S.; Ishiguro, N. Prognostic value of indoleamine 2,3-dioxygenase expression in high grade osteosarcoma. Clin. Exp. Metastasis,  2009, 26(8), 1005-1012.
 [http://dx.doi.org/10.1007/s10585-009-9290-7] [PMID:  19802733]

[90]
Chapoval, A.I.; Ni, J.; Lau, J.S.; Wilcox, R.A.; Flies, D.B.; Liu, D.; Dong, H.; Sica, G.L.; Zhu, G.; Tamada, K.; Chen, L. B7-H3: A costimulatory molecule for T cell activation and IFN-γ production. Nat. Immunol.,  2001, 2(3), 269-274.
 [http://dx.doi.org/10.1038/85339] [PMID:  11224528]

[91]
Sun, J.; Fu, F.; Gu, W.; Yan, R.; Zhang, G.; Shen, Z.; Zhou, Y.; Wang, H.; Shen, B.; Zhang, X. Origination of new immunological functions in the costimulatory molecule B7-H3: the role of exon duplication in evolution of the immune system. PLoS One,  2011, 6(9), e24751.
 [http://dx.doi.org/10.1371/journal.pone.0024751] [PMID:  21931843]

[92]
Ling, V.; Wu, P.W.; Spaulding, V.; Kieleczawa, J.; Luxenberg, D.; Carreno, B.M.; Collins, M. Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like domains: divergent history of functional redundancy and exon loss. Genomics,  2003, 82(3), 365-377.
 [http://dx.doi.org/10.1016/S0888-7543(03)00126-5] [PMID:  12906861]

[93]
Steinberger, P.; Majdic, O.; Derdak, S.V.; Pfistershammer, K.; Kirchberger, S.; Klauser, C.; Zlabinger, G.; Pickl, W.F.; Stöckl, J.; Knapp, W. Molecular characterization of human 4Ig-B7-H3, a member of the B7 family with four Ig-like domains. J. Immunol.,  2004, 172(4), 2352-2359.
 [http://dx.doi.org/10.4049/jimmunol.172.4.2352] [PMID:  14764704]

[94]
Sun, M.; Richards, S.; Prasad, D.V.R.; Mai, X.M.; Rudensky, A.; Dong, C. Characterization of mouse and human B7-H3 genes. J. Immunol.,  2002, 168(12), 6294-6297.
 [http://dx.doi.org/10.4049/jimmunol.168.12.6294] [PMID:  12055244]

[95]
Zhou, Y.H.; Chen, Y.J.; Ma, Z.Y.; Xu, L.; Wang, Q.; Zhang, G.B.; Xie, F.; Ge, Y.; Wang, X.F.; Zhang, X.G. 4IgB7-H3 is the major isoform expressed on immunocytes as well as malignant cells. Tissue Antigens,  2007, 70(2), 96-104.
 [http://dx.doi.org/10.1111/j.1399-0039.2007.00853.x] [PMID:  17610414]

[96]
Zhang, G.; Hou, J.; Shi, J.; Yu, G.; Lu, B.; Zhang, X. Soluble CD276 (B7-H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum. Immunology,  2008, 123(4), 538-546.
 [http://dx.doi.org/10.1111/j.1365-2567.2007.02723.x] [PMID:  18194267]

[97]
Picarda, E.; Ohaegbulam, K.C.; Zang, X. Molecular Pathways: Targeting B7-H3 (CD276) for Human Cancer Immunotherapy. Clin. Cancer Res.,  2016, 22(14), 3425-3431.
 [http://dx.doi.org/10.1158/1078-0432.CCR-15-2428] [PMID:  27208063]

[98]
Carreno, B.M.; Collins, M. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Annu. Rev. Immunol.,  2002, 20(1), 29-53.
 [http://dx.doi.org/10.1146/annurev.immunol.20.091101.091806] [PMID:  11861596]

[99]
Chen, L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat. Rev. Immunol.,  2004, 4(5), 336-347.
 [http://dx.doi.org/10.1038/nri1349] [PMID:  15122199]

[100]
Greenwald, R.J.; Freeman, G.J.; Sharpe, A.H. The B7 family revisited. Annu. Rev. Immunol.,  2005, 23(1), 515-548.
 [http://dx.doi.org/10.1146/annurev.immunol.23.021704.115611] [PMID:  15771580]

[101]
Hashiguchi, M.; Kobori, H.; Ritprajak, P.; Kamimura, Y.; Kozono, H.; Azuma, M. Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses. Proc. Natl. Acad. Sci. USA,  2008, 105(30), 10495-10500.
 [http://dx.doi.org/10.1073/pnas.0802423105] [PMID:  18650384]

[102]
Prasad, D.V.R.; Nguyen, T.; Li, Z.; Yang, Y.; Duong, J.; Wang, Y.; Dong, C. Murine B7-H3 is a negative regulator of T cells. J. Immunol.,  2004, 173(4), 2500-2506.
 [http://dx.doi.org/10.4049/jimmunol.173.4.2500] [PMID:  15294965]

[103]
Mahnke, K.; Ring, S.; Johnson, T.S.; Schallenberg, S.; Schönfeld, K.; Storn, V.; Bedke, T.; Enk, A.H. Induction of immunosuppressive functions of dendritic cells in vivo by CD4+CD25+ regulatory T cells: Role of B7-H3 expression and antigen presentation. Eur. J. Immunol.,  2007, 37(8), 2117-2126.
 [http://dx.doi.org/10.1002/eji.200636841] [PMID:  17615586]

[104]
Leitner, J.; Klauser, C.; Pickl, W.F.; Stöckl, J.; Majdic, O.; Bardet, A.F.; Kreil, D.P.; Dong, C.; Yamazaki, T.; Zlabinger, G.; Pfistershammer, K.; Steinberger, P. B7-H3 is a potent inhibitor of human T-cell activation: No evidence for B7-H3 and TREML2 interaction. Eur. J. Immunol.,  2009, 39(7), 1754-1764.
 [http://dx.doi.org/10.1002/eji.200839028] [PMID:  19544488]

[105]
Hofmeyer, K.A.; Ray, A.; Zang, X. The contrasting role of B7-H3. Proc. Natl. Acad. Sci. USA,  2008, 105(30), 10277-10278.
 [http://dx.doi.org/10.1073/pnas.0805458105] [PMID:  18650376]

[106]
Petroff, M.G.; Kharatyan, E.; Torry, D.S.; Holets, L. The immunomodulatory proteins B7-DC, B7-H2, and B7-H3 are differentially expressed across gestation in the human placenta. Am. J. Pathol.,  2005, 167(2), 465-473.
 [http://dx.doi.org/10.1016/S0002-9440(10)62990-2] [PMID:  16049332]

[107]
Wang, J.; Chong, K.K.; Nakamura, Y.; Nguyen, L.; Huang, S.K.; Kuo, C.; Zhang, W.; Yu, H.; Morton, D.L.; Hoon, D.S.B. B7-H3 associated with tumor progression and epigenetic regulatory activity in cutaneous melanoma. J. Invest. Dermatol.,  2013, 133(8), 2050-2058.
 [http://dx.doi.org/10.1038/jid.2013.114] [PMID:  23474948]

[108]
Hu, Y.; Lv, X.; Wu, Y.; Xu, J.; Wang, L.; Chen, W.; Zhang, W.; Li, J.; Zhang, S.; Qiu, H. Expression of costimulatory molecule B7-H3 and its prognostic implications in human acute leukemia. Hematology,  2015, 20(4), 187-195.
 [http://dx.doi.org/10.1179/1607845414Y.0000000186] [PMID:  25130683]

[109]
Sun, J.; Guo, Y.; Li, X.; Zhang, Y.; Gu, L.; Wu, P.; Bai, G.; Xiao, Y. B7-H3 expression in breast cancer and upregulation of VEGF through gene silence. OncoTargets Ther.,  2014, 7, 1979-1986.
 [http://dx.doi.org/10.2147/OTT.S63424] [PMID:  25378933]

[110]
Zang, X.; Thompson, R.H.; Al-Ahmadie, H.A.; Serio, A.M.; Reuter, V.E.; Eastham, J.A.; Scardino, P.T.; Sharma, P.; Allison, J.P. B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc. Natl. Acad. Sci. USA,  2007, 104(49), 19458-19463.
 [http://dx.doi.org/10.1073/pnas.0709802104] [PMID:  18042703]

[111]
Zang, X.; Sullivan, P.S.; Soslow, R.A.; Waitz, R.; Reuter, V.E.; Wilton, A. Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas. Modern pathology: an official journal of the United States and Canadian Academy of Pathology. Inc.,  2010, 23(8), 1104-1112.

[112]
Chen, Y.; Zhao, H.; Zhu, D. zhi; He, S.; Kuang, Y.; Li, D.; Zhang, Z.; Song, S.; Zhang, L.; Sun, J. The coexpression and clinical significance of costimulatory molecules B7-H1, B7-H3, and B7-H4 in human pancreatic cancer. OncoTargets Ther.,  2014, 7, 1465-1472.
 [http://dx.doi.org/10.2147/OTT.S66809] [PMID:  25170273]

[113]
Ingebrigtsen, V.A.; Boye, K.; Nesland, J.M.; Nesbakken, A.; Flatmark, K.; Fodstad, Ø. B7-H3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome. BMC Cancer,  2014, 14(1), 602.
 [http://dx.doi.org/10.1186/1471-2407-14-602] [PMID:  25139714]

[114]
Lemke, D.; Pfenning, P.N.; Sahm, F.; Klein, A.C.; Kempf, T.; Warnken, U.; Schnölzer, M.; Tudoran, R.; Weller, M.; Platten, M.; Wick, W. Costimulatory protein 4IgB7H3 drives the malignant phenotype of glioblastoma by mediating immune escape and invasiveness. Clin. Cancer Res.,  2012, 18(1), 105-117.
 [http://dx.doi.org/10.1158/1078-0432.CCR-11-0880] [PMID:  22080438]

[115]
Wang, L.; Zhang, Q.; Chen, W.; Shan, B.; Ding, Y.; Zhang, G.; Cao, N.; Liu, L.; Zhang, Y. B7-H3 is overexpressed in patients suffering osteosarcoma and associated with tumor aggressiveness and metastasis. PLoS One,  2013, 8(8), e70689.
 [http://dx.doi.org/10.1371/journal.pone.0070689] [PMID:  23940627]

[116]
Ingebrigtsen, V.A.; Boye, K.; Tekle, C.; Nesland, J.M.; Flatmark, K.; Fodstad, Ø. B7-H3 expression in colorectal cancer: Nuclear localization strongly predicts poor outcome in colon cancer. Int. J. Cancer,  2012, 131(11), 2528-2536.
 [http://dx.doi.org/10.1002/ijc.27566] [PMID:  22473715]

[117]
Qin, X.; Zhang, H.; Ye, D.; Dai, B.; Zhu, Y.; Shi, G. B7-H3 is a new cancer-specific endothelial marker in clear cell renal cell carcinoma. OncoTargets Ther.,  2013, 6, 1667-1673.
 [http://dx.doi.org/10.2147/OTT.S53565] [PMID:  24265557]

[118]
Bachawal, S.V.; Jensen, K.C.; Wilson, K.E.; Tian, L.; Lutz, A.M.; Willmann, J.K. Breast cancer detection by B7-H3-targeted ultrasound molecular imaging. Cancer Res.,  2015, 75(12), 2501-2509.
 [http://dx.doi.org/10.1158/0008-5472.CAN-14-3361] [PMID:  25899053]

[119]
Arigami, T.; Narita, N.; Mizuno, R.; Nguyen, L.; Ye, X.; Chung, A.; Giuliano, A.E.; Hoon, D.S.B. B7-h3 ligand expression by primary breast cancer and associated with regional nodal metastasis. Ann. Surg.,  2010, 252(6), 1044-1051.
 [http://dx.doi.org/10.1097/SLA.0b013e3181f1939d] [PMID:  21107115]

[120]
Kraan, J.; van den Broek, P.; Verhoef, C.; Grunhagen, D.J.; Taal, W.; Gratama, J.W.; Sleijfer, S. Endothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells. Br. J. Cancer,  2014, 111(1), 149-156.
 [http://dx.doi.org/10.1038/bjc.2014.286] [PMID:  24892449]

[121]
Liu, C.; Liu, J.; Wang, J.; Liu, Y.; Zhang, F.; Lin, W.; Gao, A.; Sun, M.; Wang, Y.; Sun, Y. B7-H3 expression in ductal and lobular breast cancer and its association with IL-10. Mol. Med. Rep.,  2013, 7(1), 134-138.
 [http://dx.doi.org/10.3892/mmr.2012.1158] [PMID:  23128494]

[122]
Loo, D.; Alderson, R.F.; Chen, F.Z.; Huang, L.; Zhang, W.; Gorlatov, S.; Burke, S.; Ciccarone, V.; Li, H.; Yang, Y.; Son, T.; Chen, Y.; Easton, A.N.; Li, J.C.; Rillema, J.R.; Licea, M.; Fieger, C.; Liang, T.W.; Mather, J.P.; Koenig, S.; Stewart, S.J.; Johnson, S.; Bonvini, E.; Moore, P.A. Development of an Fc-enhanced anti-B7-H3 monoclonal antibody with potent antitumor activity. Clin. Cancer Res.,  2012, 18(14), 3834-3845.
 [http://dx.doi.org/10.1158/1078-0432.CCR-12-0715] [PMID:  22615450]

[123]
Maeda, N.; Yoshimura, K.; Yamamoto, S.; Kuramasu, A.; Inoue, M.; Suzuki, N.; Watanabe, Y.; Maeda, Y.; Kamei, R.; Tsunedomi, R.; Shindo, Y.; Inui, M.; Tamada, K.; Yoshino, S.; Hazama, S.; Oka, M. Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients. Ann. Surg. Oncol.,  2014, 21(S4)(Suppl. 4), 546-554.
 [http://dx.doi.org/10.1245/s10434-014-3564-2] [PMID:  24562936]

[124]
Chen, J.T.; Chen, C.H.; Ku, K.L.; Hsiao, M.; Chiang, C.P.; Hsu, T.L.; Chen, M.H.; Wong, C.H. Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and immune response. Proc. Natl. Acad. Sci. USA,  2015, 112(42), 13057-13062.
 [http://dx.doi.org/10.1073/pnas.1516991112] [PMID:  26438868]

[125]
Biglarian, A.; Hajizadeh, E.; Kazemnejad, A.; Zayeri, F. Determining of prognostic factors in gastric cancer patients using artificial neural networks. APJCP,  2010, 11(2), 533-536.
 [PMID:  20843146]

[126]
Sun, Y.; Wang, Y.; Zhao, J.; Gu, M.; Giscombe, R.; Lefvert, A.K.; Wang, X. B7-H3 and B7-H4 expression in non-small-cell lung cancer. Lung Cancer,  2006, 53(2), 143-151.
 [http://dx.doi.org/10.1016/j.lungcan.2006.05.012] [PMID:  16782226]

[127]
Chen, C.; Shen, Y.; Qu, Q.X.; Chen, X.Q.; Zhang, X.G.; Huang, J.A. Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response. Exp. Cell Res.,  2013, 319(1), 96-102.
 [http://dx.doi.org/10.1016/j.yexcr.2012.09.006] [PMID:  22999863]

[128]
Lupu, C.M.; Eisenbach, C.; Kuefner, M.A.; Schmidt, J.; Lupu, A.D.; Stremmel, W.; Encke, J. An orthotopic colon cancer model for studying the B7-H3 antitumor effect in vivo. J. Gastrointest. Surg.,  2006, 10(5), 635-645.
 [http://dx.doi.org/10.1007/BF03239969] [PMID:  16713537]

[129]
Zhang, W.; Wang, J.; Wang, Y.; Dong, F.; Zhu, M.; Wan, W.; Li, H.; Wu, F.; Yan, X.; Ke, X. B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells. OncoTargets Ther.,  2015, 8, 1721-1733.
 [http://dx.doi.org/10.2147/OTT.S85272] [PMID:  26203263]

[130]
Shapiro, S.D. Matrix metalloproteinase degradation of extracellular matrix: biological consequences. Curr. Opin. Cell Biol.,  1998, 10(5), 602-608.
 [http://dx.doi.org/10.1016/S0955-0674(98)80035-5] [PMID:  9818170]

[131]
Chen, Y.W.; Tekle, C.; Fodstad, O. The immunoregulatory protein human B7H3 is a tumor-associated antigen that regulates tumor cell migration and invasion. Curr. Cancer Drug Targets,  2008, 8(5), 404-413.
 [http://dx.doi.org/10.2174/156800908785133141] [PMID:  18690846]

[132]
Liu, F.; Zhang, T.; Zou, S.; Jiang, B.; Hua, D. B7-H3 promotes cell migration and invasion through the Jak2/Stat3/MMP9 signaling pathway in colorectal cancer. Mol. Med. Rep.,  2015, 12(4), 5455-5460.
 [http://dx.doi.org/10.3892/mmr.2015.4050] [PMID:  26151358]

[133]
Liu, H.; Tekle, C.; Chen, Y.W.; Kristian, A.; Zhao, Y.; Zhou, M.; Liu, Z.; Ding, Y.; Wang, B.; Mælandsmo, G.M.; Nesland, J.M.; Fodstad, O.; Tan, M. B7-H3 silencing increases paclitaxel sensitivity by abrogating Jak2/Stat3 phosphorylation. Mol. Cancer Ther.,  2011, 10(6), 960-971.
 [http://dx.doi.org/10.1158/1535-7163.MCT-11-0072] [PMID:  21518725]

[134]
Zhang, T.; Jiang, B.; Zou, S.T.; Liu, F.; Hua, D. Overexpression of B7-H3 augments anti-apoptosis of colorectal cancer cells by Jak2-STAT3. World J. Gastroenterol.,  2015, 21(6), 1804-1813.
 [http://dx.doi.org/10.3748/wjg.v21.i6.1804] [PMID:  25684945]

[135]
Kang, F.; Wang, L.; Jia, H.; Li, D.; Li, H.; Zhang, Y.; Sun, D. B7-H3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-to-mesenchymal transition via JAK2/STAT3/Slug signaling pathway. Cancer Cell Int.,  2015, 15(1), 45.
 [http://dx.doi.org/10.1186/s12935-015-0195-z] [PMID:  25908926]

[136]
Tekle, C.; Nygren, M.K.; Chen, Y.W.; Dybsjord, I.; Nesland, J.M.; Maelandsmo, G.M.; Fodstad, Ø. B7-H3 contributes to the metastatic capacity of melanoma cells by modulation of known metastasis-associated genes. Int. J. Cancer,  2012, 130(10), 2282-2290.
 [http://dx.doi.org/10.1002/ijc.26238] [PMID:  21671471]

[137]
Xu, L.; Ding, X.; Tan, H.; Qian, J. Correlation between B7-H3 expression and matrix metalloproteinases 2 expression in pancreatic cancer. Cancer Cell Int.,  2013, 13(1), 81.
 [http://dx.doi.org/10.1186/1475-2867-13-81] [PMID:  23947693]

[138]
Nunes-Xavier, C.E.; Karlsen, K.F.; Tekle, C.; Pedersen, C.; Øyjord, T.; Hongisto, V.; Nesland, J.M.; Tan, M.; Sahlberg, K.K.; Fodstad, Ø. Decreased expression of B7-H3 reduces the glycolytic capacity and sensitizes breast cancer cells to AKT/mTOR inhibitors. Oncotarget,  2016, 7(6), 6891-6901.
 [http://dx.doi.org/10.18632/oncotarget.6902] [PMID:  26771843]

[139]
Lim, S.; Liu, H.; da Silva, L.M.; Arora, R.; Liu, Z.; Phillips, J.B.; Schmitt, D.C.; Vu, T.; McClellan, S.; Lin, Y.; Lin, W.; Piazza, G.A.; Fodstad, O.; Tan, M. Immunoregulatory protein B7-H3 reprograms glucose metabolism in cancer cells by ROS-mediated stabilization of HIF1α. Cancer Res.,  2016, 76(8), 2231-2242.
 [http://dx.doi.org/10.1158/0008-5472.CAN-15-1538] [PMID:  27197253]

[140]
Luther, N.; Zhou, Z.; Zanzonico, P.; Cheung, N.K.; Humm, J.; Edgar, M.A. The potential of theragnostic (1)(2)(4)I-8H9 convection-enhanced delivery in diffuse intrinsic pontine glioma. Neuro-oncol.,  2014, 16(6), 800-806.
 [http://dx.doi.org/10.1093/neuonc/not298] [PMID:  24526309]

[141]
Modak, S.; Guo, H.F.; Humm, J.L.; Smith-Jones, P.M.; Larson, S.M.; Cheung, N.K.V. Radioimmunotargeting of human rhabdomyosarcoma using monoclonal antibody 8H9. Cancer Biother. Radiopharm.,  2005, 20(5), 534-546.
 [http://dx.doi.org/10.1089/cbr.2005.20.534] [PMID:  16248769]

[142]
Ahmed, M.; Cheng, M.; Zhao, Q.; Goldgur, Y.; Cheal, S.M.; Guo, H.F.; Larson, S.M.; Cheung, N.K.V. Humanized Affinity-matured monoclonal antibody 8H9 has potent antitumor activity and binds to FG loop of tumor antigen B7-H3. J. Biol. Chem.,  2015, 290(50), 30018-30029.
 [http://dx.doi.org/10.1074/jbc.M115.679852] [PMID:  26487718]

[143]
Kramer, K.; Kushner, B.H.; Modak, S.; Pandit-Taskar, N.; Smith-Jones, P.; Zanzonico, P.; Humm, J.L.; Xu, H.; Wolden, S.L.; Souweidane, M.M.; Larson, S.M.; Cheung, N.K.V. Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma. J. Neurooncol.,  2010, 97(3), 409-418.
 [http://dx.doi.org/10.1007/s11060-009-0038-7] [PMID:  19890606]

[144]
Shi, Z.; Hu, Y.; Chen, H.; Fu, F.; Zhang, X. Identification and characterization of monoclonal antibody Y4F11 against human B7-H3. XiBao Yu FenZi Mian Yi X ue ZaZ hi,  2016, 32(10), 1402-1406.

[145]
Xu, H.; Cheung, I.Y.; Guo, H.F.; Cheung, N.K.V. MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. Cancer Res.,  2009, 69(15), 6275-6281.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-4517] [PMID:  19584290]

[146]
Li, B.; VanRoey, M.; Triebel, F.; Jooss, K. Lymphocyte activation gene-3 fusion protein increases the potency of a granulocyte macrophage colony-stimulating factor-secreting tumor cell immunotherapy. Clin. Cancer Res.,  2008, 14(11), 3545-3554.
 [http://dx.doi.org/10.1158/1078-0432.CCR-07-5200] [PMID:  18519788]

[147]
Yan, J.; Kong, L.Y.; Hu, J.; Gabrusiewicz, K.; Dibra, D.; Xia, X.; Heimberger, A.B.; Li, S. FGL2 as a multimodality regulator of tumor-mediated immune suppression and therapeutic target in gliomas. J. Natl. Cancer Inst.,  2015, 107(8), djv137.
 [http://dx.doi.org/10.1093/jnci/djv137] [PMID:  25971300]

[148]
Sakuishi, K.; Apetoh, L.; Sullivan, J.M.; Blazar, B.R.; Kuchroo, V.K.; Anderson, A.C. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J. Exp. Med.,  2010, 207(10), 2187-2194.
 [http://dx.doi.org/10.1084/jem.20100643] [PMID:  20819927]

[149]
Wang, L.; Rubinstein, R.; Lines, J.L.; Wasiuk, A.; Ahonen, C.; Guo, Y.; Lu, L.F.; Gondek, D.; Wang, Y.; Fava, R.A.; Fiser, A.; Almo, S.; Noelle, R.J. VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J. Exp. Med.,  2011, 208(3), 577-592.
 [http://dx.doi.org/10.1084/jem.20100619] [PMID:  21383057]

[150]
Fan, X.; Quezada, S.A.; Sepulveda, M.A.; Sharma, P.; Allison, J.P. Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy. J. Exp. Med.,  2014, 211(4), 715-725.
 [http://dx.doi.org/10.1084/jem.20130590] [PMID:  24687957]

[151]
Curti, B.D.; Kovacsovics-Bankowski, M.; Morris, N.; Walker, E.; Chisholm, L.; Floyd, K.; Walker, J.; Gonzalez, I.; Meeuwsen, T.; Fox, B.A.; Moudgil, T.; Miller, W.; Haley, D.; Coffey, T.; Fisher, B.; Delanty-Miller, L.; Rymarchyk, N.; Kelly, T.; Crocenzi, T.; Bernstein, E.; Sanborn, R.; Urba, W.J.; Weinberg, A.D. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res.,  2013, 73(24), 7189-7198.
 [http://dx.doi.org/10.1158/0008-5472.CAN-12-4174] [PMID:  24177180]

[152]
Melero, I.; Shuford, W.W.; Newby, S.A.; Aruffo, A.; Ledbetter, J.A.; Hellström, K.E.; Mittler, R.S.; Chen, L. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat. Med.,  1997, 3(6), 682-685.
 [http://dx.doi.org/10.1038/nm0697-682] [PMID:  9176498]

[153]
Janjigian, Y.Y.; Shitara, K.; Moehler, M.; Garrido, M.; Salman, P.; Shen, L.; Wyrwicz, L.; Yamaguchi, K.; Skoczylas, T.; Campos Bragagnoli, A.; Liu, T.; Schenker, M.; Yanez, P.; Tehfe, M.; Kowalyszyn, R.; Karamouzis, M.V.; Bruges, R.; Zander, T.; Pazo-Cid, R.; Hitre, E.; Feeney, K.; Cleary, J.M.; Poulart, V.; Cullen, D.; Lei, M.; Xiao, H.; Kondo, K.; Li, M.; Ajani, J.A. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet,  2021, 398(10294), 27-40.
 [http://dx.doi.org/10.1016/S0140-6736(21)00797-2] [PMID:  34102137]

[154]
Migden, M.R.; Rischin, D.; Schmults, C.D.; Guminski, A.; Hauschild, A.; Lewis, K.D.; Chung, C.H.; Hernandez-Aya, L.; Lim, A.M.; Chang, A.L.S.; Rabinowits, G.; Thai, A.A.; Dunn, L.A.; Hughes, B.G.M.; Khushalani, N.I.; Modi, B.; Schadendorf, D.; Gao, B.; Seebach, F.; Li, S.; Li, J.; Mathias, M.; Booth, J.; Mohan, K.; Stankevich, E.; Babiker, H.M.; Brana, I.; Gil-Martin, M.; Homsi, J.; Johnson, M.L.; Moreno, V.; Niu, J.; Owonikoko, T.K.; Papadopoulos, K.P.; Yancopoulos, G.D.; Lowy, I.; Fury, M.G. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N. Engl. J. Med.,  2018, 379(4), 341-351.
 [http://dx.doi.org/10.1056/NEJMoa1805131] [PMID:  29863979]

[155]
Cho, B.C.; Abreu, D.R.; Hussein, M.; Cobo, M.; Patel, A.J.; Secen, N.; Lee, K.H.; Massuti, B.; Hiret, S.; Yang, J.C.H.; Barlesi, F.; Lee, D.H.; Ares, L.P.; Hsieh, R.W.; Patil, N.S.; Twomey, P.; Yang, X.; Meng, R.; Johnson, M.L. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol.,  2022, 23(6), 781-792.
 [http://dx.doi.org/10.1016/S1470-2045(22)00226-1] [PMID:  35576957]

[156]
Powles, T.; Park, S.H.; Voog, E.; Caserta, C.; Valderrama, B.P.; Gurney, H.; Kalofonos, H. Radulović S.; Demey, W.; Ullén, A.; Loriot, Y.; Sridhar, S.S.; Tsuchiya, N.; Kopyltsov, E.; Sternberg, C.N.; Bellmunt, J.; Aragon-Ching, J.B.; Petrylak, D.P.; Laliberte, R.; Wang, J.; Huang, B.; Davis, C.; Fowst, C.; Costa, N.; Blake-Haskins, J.A.; di Pietro, A.; Grivas, P. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N. Engl. J. Med.,  2020, 383(13), 1218-1230.
 [http://dx.doi.org/10.1056/NEJMoa2002788] [PMID:  32945632]

[157]
Rizzo, A.; Ricci, A.D.; Brandi, G. Durvalumab: an investigational anti-PD-L1 antibody for the treatment of biliary tract cancer. Expert Opin. Investig. Drugs,  2021, 30(4), 343-350.
 [http://dx.doi.org/10.1080/13543784.2021.1897102] [PMID:  33645367]

[158]
Wolchok, J.D.; Kluger, H.; Callahan, M.K.; Postow, M.A.; Rizvi, N.A.; Lesokhin, A.M.; Segal, N.H.; Ariyan, C.E.; Gordon, R.A.; Reed, K.; Burke, M.M.; Caldwell, A.; Kronenberg, S.A.; Agunwamba, B.U.; Zhang, X.; Lowy, I.; Inzunza, H.D.; Feely, W.; Horak, C.E.; Hong, Q.; Korman, A.J.; Wigginton, J.M.; Gupta, A.; Sznol, M. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med.,  2013, 369(2), 122-133.
 [http://dx.doi.org/10.1056/NEJMoa1302369] [PMID:  23724867]

[159]
Kelley, R.K.; Sangro, B.; Harris, W.; Ikeda, M.; Okusaka, T.; Kang, Y.K.; Qin, S.; Tai, D.W.M.; Lim, H.Y.; Yau, T.; Yong, W.P.; Cheng, A.L.; Gasbarrini, A.; Damian, S.; Bruix, J.; Borad, M.; Bendell, J.; Kim, T.Y.; Standifer, N.; He, P.; Makowsky, M.; Negro, A.; Kudo, M.; Abou-Alfa, G.K. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I/II study. J. Clin. Oncol.,  2021, 39(27), 2991-3001.
 [http://dx.doi.org/10.1200/JCO.20.03555] [PMID:  34292792]

[160]
Sordo-Bahamonde, C.; Lorenzo-Herrero, S.; González-Rodríguez, A.P.; Payer, Á.R.; González-García, E.; López-Soto, A.; Gonzalez, S. LAG-3 blockade with relatlimab (BMS-986016) restores anti-leukemic responses in chronic lymphocytic leukemia. Cancers (Basel),  2021, 13(9), 2112.
 [http://dx.doi.org/10.3390/cancers13092112] [PMID:  33925565]

[161]
Chocarro, L.; Bocanegra, A.; Blanco, E.; Fernández-Rubio, L.; Arasanz, H.; Echaide, M.; Garnica, M.; Ramos, P.; Piñeiro-Hermida, S.; Vera, R.; Escors, D.; Kochan, G. Cutting-Edge: preclinical and clinical development of the first approved Lag-3 inhibitor. Cells,  2022, 11(15), 2351.
 [http://dx.doi.org/10.3390/cells11152351] [PMID:  35954196]

[162]
Kumar, S.; Jaipuri, F.A.; Waldo, J.P.; Potturi, H.; Marcinowicz, A.; Adams, J.; Van Allen, C.; Zhuang, H.; Vahanian, N.; Link, C., Jr; Brincks, E.L.; Mautino, M.R. Discovery of indoximod prodrugs and characterization of clinical candidate NLG802. Eur. J. Med. Chem.,  2020, 198, 112373.
 [http://dx.doi.org/10.1016/j.ejmech.2020.112373] [PMID:  32422549]

[163]
Long, G.V.; Dummer, R.; Hamid, O.; Gajewski, T.F.; Caglevic, C.; Dalle, S.; Arance, A.; Carlino, M.S.; Grob, J.J.; Kim, T.M.; Demidov, L.; Robert, C.; Larkin, J.; Anderson, J.R.; Maleski, J.; Jones, M.; Diede, S.J.; Mitchell, T.C. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol.,  2019, 20(8), 1083-1097.
 [http://dx.doi.org/10.1016/S1470-2045(19)30274-8] [PMID:  31221619]

[164]
Nayak-Kapoor, A.; Hao, Z.; Sadek, R.; Dobbins, R.; Marshall, L.; Vahanian, N.N.; Jay Ramsey, W.; Kennedy, E.; Mautino, M.R.; Link, C.J.; Lin, R.S.; Royer-Joo, S.; Liang, X.; Salphati, L.; Morrissey, K.M.; Mahrus, S.; McCall, B.; Pirzkall, A.; Munn, D.H.; Janik, J.E.; Khleif, S.N. Phase Ia study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) in patients with recurrent advanced solid tumors. J. Immunother. Cancer,  2018, 6(1), 61.
 [http://dx.doi.org/10.1186/s40425-018-0351-9] [PMID:  29921320]

[165]
Ferris, R.L.; Jaffee, E.M.; Ferrone, S. Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical response, cellular immunity, and immunoescape. J. Clin. Oncol.,  2010, 28(28), 4390-4399.
 [http://dx.doi.org/10.1200/JCO.2009.27.6360] [PMID:  20697078]

[166]
Okada, H.; Low, K.L.; Kohanbash, G.; McDonald, H.A.; Hamilton, R.L.; Pollack, I.F. Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas. J. Neurooncol.,  2008, 88(3), 245-250.
 [http://dx.doi.org/10.1007/s11060-008-9566-9] [PMID:  18324354]

[167]
Yang, M.; Xie, W.; Mostaghel, E.; Nakabayashi, M.; Werner, L.; Sun, T.; Pomerantz, M.; Freedman, M.; Ross, R.; Regan, M.; Sharifi, N.; Figg, W.D.; Balk, S.; Brown, M.; Taplin, M.E.; Oh, W.K.; Lee, G.S.M.; Kantoff, P.W. SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. J. Clin. Oncol.,  2011, 29(18), 2565-2573.
 [http://dx.doi.org/10.1200/JCO.2010.31.2405] [PMID:  21606417]

[168]
Zhu, Z.; Zhong, S.; Shen, Z. Targeting the inflammatory pathways to enhance chemotherapy of cancer. Cancer Biol. Ther.,  2011, 12(2), 95-105.
 [http://dx.doi.org/10.4161/cbt.12.2.15952] [PMID:  21623164]

[169]
Curtin, J.; King, G.; Candolfi, M.; Greeno, R.; Kroeger, K.; Lowenstein, P.; Castro, M. Combining cytotoxic and immune-mediated gene therapy to treat brain tumors. Curr. Top. Med. Chem.,  2005, 5(12), 1151-1170.
 [http://dx.doi.org/10.2174/156802605774370856] [PMID:  16248789]

[170]
Ohm, J.E.; McGarvey, K.M.; Yu, X.; Cheng, L.; Schuebel, K.E.; Cope, L.; Mohammad, H.P.; Chen, W.; Daniel, V.C.; Yu, W.; Berman, D.M.; Jenuwein, T.; Pruitt, K.; Sharkis, S.J.; Watkins, D.N.; Herman, J.G.; Baylin, S.B. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat. Genet.,  2007, 39(2), 237-242.
 [http://dx.doi.org/10.1038/ng1972] [PMID:  17211412]

[171]
Haberland, M.; Montgomery, R.L.; Olson, E.N. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat. Rev. Genet.,  2009, 10(1), 32-42.
 [http://dx.doi.org/10.1038/nrg2485] [PMID:  19065135]

[172]
Shi, Y. Histone lysine demethylases: emerging roles in development, physiology and disease. Nat. Rev. Genet.,  2007, 8(11), 829-833.
 [http://dx.doi.org/10.1038/nrg2218] [PMID:  17909537]

[173]
Lucio-Eterovic, A.K.B.; Cortez, M.A.A.; Valera, E.T.; Motta, F.J.N.; Queiroz, R.G.P.; Machado, H.R.; Carlotti, C.G., Jr; Neder, L.; Scrideli, C.A.; Tone, L.G. Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas. BMC Cancer,  2008, 8(1), 243.
 [http://dx.doi.org/10.1186/1471-2407-8-243] [PMID:  18713462]

[174]
Parsons, D.W.; Jones, S.; Zhang, X.; Lin, J.C.H.; Leary, R.J.; Angenendt, P.; Mankoo, P.; Carter, H.; Siu, I.M.; Gallia, G.L.; Olivi, A.; McLendon, R.; Rasheed, B.A.; Keir, S.; Nikolskaya, T.; Nikolsky, Y.; Busam, D.A.; Tekleab, H.; Diaz, L.A., Jr; Hartigan, J.; Smith, D.R.; Strausberg, R.L.; Marie, S.K.N.; Shinjo, S.M.O.; Yan, H.; Riggins, G.J.; Bigner, D.D.; Karchin, R.; Papadopoulos, N.; Parmigiani, G.; Vogelstein, B.; Velculescu, V.E.; Kinzler, K.W. An integrated genomic analysis of human glioblastoma multiforme. Science,  2008, 321(5897), 1807-1812.
 [http://dx.doi.org/10.1126/science.1164382] [PMID:  18772396]

[175]
Leung, C.; Lingbeek, M.; Shakhova, O.; Liu, J.; Tanger, E.; Saremaslani, P.; van Lohuizen, M.; Marino, S. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature,  2004, 428(6980), 337-341.
 [http://dx.doi.org/10.1038/nature02385] [PMID:  15029199]

[176]
Milde, T.; Oehme, I.; Korshunov, A.; Kopp-Schneider, A.; Remke, M.; Northcott, P.; Deubzer, H.E.; Lodrini, M.; Taylor, M.D.; von Deimling, A.; Pfister, S.; Witt, O. HDAC5 and HDAC9 in medulloblastoma: novel markers for risk stratification and role in tumor cell growth. Clin. Cancer Res.,  2010, 16(12), 3240-3252.
 [http://dx.doi.org/10.1158/1078-0432.CCR-10-0395] [PMID:  20413433]

[177]
Sturm, D.; Bender, S.; Jones, D.T.W.; Lichter, P.; Grill, J.; Becher, O.; Hawkins, C.; Majewski, J.; Jones, C.; Costello, J.F.; Iavarone, A.; Aldape, K.; Brennan, C.W.; Jabado, N.; Pfister, S.M. Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat. Rev. Cancer,  2014, 14(2), 92-107.
 [http://dx.doi.org/10.1038/nrc3655] [PMID:  24457416]

[178]
Wu, G.; Broniscer, A.; McEachron, T.A.; Lu, C.; Paugh, B.S.; Becksfort, J.; Qu, C.; Ding, L.; Huether, R.; Parker, M.; Zhang, J.; Gajjar, A.; Dyer, M.A.; Mullighan, C.G.; Gilbertson, R.J.; Mardis, E.R.; Wilson, R.K.; Downing, J.R.; Ellison, D.W.; Zhang, J.; Baker, S.J. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat. Genet.,  2012, 44(3), 251-253.
 [http://dx.doi.org/10.1038/ng.1102] [PMID:  22286216]

[179]
Buczkowicz, P.; Hoeman, C.; Rakopoulos, P.; Pajovic, S.; Letourneau, L.; Dzamba, M.; Morrison, A.; Lewis, P.; Bouffet, E.; Bartels, U.; Zuccaro, J.; Agnihotri, S.; Ryall, S.; Barszczyk, M.; Chornenkyy, Y.; Bourgey, M.; Bourque, G.; Montpetit, A.; Cordero, F.; Castelo-Branco, P.; Mangerel, J.; Tabori, U.; Ho, K.C.; Huang, A.; Taylor, K.R.; Mackay, A.; Bendel, A.E.; Nazarian, J.; Fangusaro, J.R.; Karajannis, M.A.; Zagzag, D.; Foreman, N.K.; Donson, A.; Hegert, J.V.; Smith, A.; Chan, J.; Lafay-Cousin, L.; Dunn, S.; Hukin, J.; Dunham, C.; Scheinemann, K.; Michaud, J.; Zelcer, S.; Ramsay, D.; Cain, J.; Brennan, C.; Souweidane, M.M.; Jones, C.; Allis, C.D.; Brudno, M.; Becher, O.; Hawkins, C. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat. Genet.,  2014, 46(5), 451-456.
 [http://dx.doi.org/10.1038/ng.2936] [PMID:  24705254]

[180]
Fontebasso, A.M.; Papillon-Cavanagh, S.; Schwartzentruber, J.; Nikbakht, H.; Gerges, N.; Fiset, P.O.; Bechet, D.; Faury, D.; De Jay, N.; Ramkissoon, L.A.; Corcoran, A.; Jones, D.T.W.; Sturm, D.; Johann, P.; Tomita, T.; Goldman, S.; Nagib, M.; Bendel, A.; Goumnerova, L.; Bowers, D.C.; Leonard, J.R.; Rubin, J.B.; Alden, T.; Browd, S.; Geyer, J.R.; Leary, S.; Jallo, G.; Cohen, K.; Gupta, N.; Prados, M.D.; Carret, A.S.; Ellezam, B.; Crevier, L.; Klekner, A.; Bognar, L.; Hauser, P.; Garami, M.; Myseros, J.; Dong, Z.; Siegel, P.M.; Malkin, H.; Ligon, A.H.; Albrecht, S.; Pfister, S.M.; Ligon, K.L.; Majewski, J.; Jabado, N.; Kieran, M.W. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat. Genet.,  2014, 46(5), 462-466.
 [http://dx.doi.org/10.1038/ng.2950] [PMID:  24705250]

[181]
Taylor, K.R.; Mackay, A.; Truffaux, N.; Butterfield, Y.S.; Morozova, O.; Philippe, C.; Castel, D.; Grasso, C.S.; Vinci, M.; Carvalho, D.; Carcaboso, A.M.; de Torres, C.; Cruz, O.; Mora, J.; Entz-Werle, N.; Ingram, W.J.; Monje, M.; Hargrave, D.; Bullock, A.N.; Puget, S.; Yip, S.; Jones, C.; Grill, J. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat. Genet.,  2014, 46(5), 457-461.
 [http://dx.doi.org/10.1038/ng.2925] [PMID:  24705252]

[182]
Wu, G.; Diaz, A.K.; Paugh, B.S.; Rankin, S.L.; Ju, B.; Li, Y.; Zhu, X.; Qu, C.; Chen, X.; Zhang, J.; Easton, J.; Edmonson, M.; Ma, X.; Lu, C.; Nagahawatte, P.; Hedlund, E.; Rusch, M.; Pounds, S.; Lin, T.; Onar-Thomas, A.; Huether, R.; Kriwacki, R.; Parker, M.; Gupta, P.; Becksfort, J.; Wei, L.; Mulder, H.L.; Boggs, K.; Vadodaria, B.; Yergeau, D.; Russell, J.C.; Ochoa, K.; Fulton, R.S.; Fulton, L.L.; Jones, C.; Boop, F.A.; Broniscer, A.; Wetmore, C.; Gajjar, A.; Ding, L.; Mardis, E.R.; Wilson, R.K.; Taylor, M.R.; Downing, J.R.; Ellison, D.W.; Zhang, J.; Baker, S.J. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat. Genet.,  2014, 46(5), 444-450.
 [http://dx.doi.org/10.1038/ng.2938] [PMID:  24705251]

[183]
Henikoff, S.; Smith, M.M. Histone variants and epigenetics. Cold Spring Harb. Perspect. Biol.,  2015, 7(1), a019364.
 [http://dx.doi.org/10.1101/cshperspect.a019364] [PMID:  25561719]

[184]
Panagopoulos, I.; Fioretos, T.; Isaksson, M.; Samuelsson, U.; Billström, R.; Strömbeck, B.; Mitelman, F.; Johansson, B. Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13). Hum. Mol. Genet.,  2001, 10(4), 395-404.
 [http://dx.doi.org/10.1093/hmg/10.4.395] [PMID:  11157802]

[185]
Zhu, C.; Qin, Y-R.; Xie, D.; Chua, D.T.T.; Fung, J.M.; Chen, L.; Fu, L.; Hu, L.; Guan, X-Y. Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma. Oncogene,  2009, 28(31), 2821-2828.
 [http://dx.doi.org/10.1038/onc.2009.137] [PMID:  19525977]

[186]
Bracken, A.P.; Pasini, D.; Capra, M.; Prosperini, E.; Colli, E.; Helin, K. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J.,  2003, 22(20), 5323-5335.
 [http://dx.doi.org/10.1093/emboj/cdg542] [PMID:  14532106]

[187]
Miremadi, A.; Oestergaard, M.Z.; Pharoah, P.D.P.; Caldas, C. Cancer genetics of epigenetic genes. Hum. Mol. Genet.,  2007, 16(R1), R28-R49.
 [http://dx.doi.org/10.1093/hmg/ddm021] [PMID:  17613546]

[188]
Jaju, R.J.; Fidler, C.; Haas, O.A.; Strickson, A.J.; Watkins, F.; Clark, K.; Cross, N.C.; Cheng, J.F.; Aplan, P.D.; Kearney, L.; Boultwood, J.; Wainscoat, J.S. A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. Blood,  2001, 98(4), 1264-1267.
 [http://dx.doi.org/10.1182/blood.V98.4.1264] [PMID:  11493482]

[189]
Du, Y.; Carling, T.; Fang, W.; Piao, Z.; Sheu, J.C.; Huang, S. Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone/protein methyltransferase superfamily. Cancer Res.,  2001, 61(22), 8094-8099.
 [PMID:  11719434]

[190]
Italiano, A.; Attias, R.; Aurias, A.; Pérot, G.; Burel-Vandenbos, F.; Otto, J.; Venissac, N.; Pedeutour, F. Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 neocentromere and 9p23-p24 amplification including JAK2 and JMJD2C. Cancer Genet. Cytogenet.,  2006, 167(2), 122-130.
 [http://dx.doi.org/10.1016/j.cancergencyto.2006.01.004] [PMID:  16737911]

[191]
Liu, G.; Bollig-Fischer, A.; Kreike, B.; van de Vijver, M.J.; Abrams, J.; Ethier, S.P.; Yang, Z.Q. Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer. Oncogene,  2009, 28(50), 4491-4500.
 [http://dx.doi.org/10.1038/onc.2009.297] [PMID:  19784073]

[192]
Kahl, P.; Gullotti, L.; Heukamp, L.C.; Wolf, S.; Friedrichs, N.; Vorreuther, R.; Solleder, G.; Bastian, P.J.; Ellinger, J.; Metzger, E.; Schüle, R.; Buettner, R. Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res.,  2006, 66(23), 11341-11347.
 [http://dx.doi.org/10.1158/0008-5472.CAN-06-1570] [PMID:  17145880]

[193]
Ropero, S.; Fraga, M.F.; Ballestar, E.; Hamelin, R.; Yamamoto, H.; Boix-Chornet, M.; Caballero, R.; Alaminos, M.; Setien, F.; Paz, M.F.; Herranz, M.; Palacios, J.; Arango, D.; Orntoft, T.F.; Aaltonen, L.A.; Schwartz, S., Jr; Esteller, M. A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. Nat. Genet.,  2006, 38(5), 566-569.
 [http://dx.doi.org/10.1038/ng1773] [PMID:  16642021]

[194]
Faria, C.M.C.; Rutka, J.T.; Smith, C.; Kongkham, P. Epigenetic mechanisms regulating neural development and pediatric brain tumor formation. J. Neurosurg. Pediatr.,  2011, 8(2), 119-132.
 [http://dx.doi.org/10.3171/2011.5.PEDS1140] [PMID:  21806352]

[195]
Grossniklaus, U.; Paro, R. Transcriptional silencing by polycomb-group proteins. Cold Spring Harb. Perspect. Biol.,  2014, 6(11), a019331.
 [http://dx.doi.org/10.1101/cshperspect.a019331] [PMID:  25367972]

[196]
Lewis, P.W.; Müller, M.M.; Koletsky, M.S.; Cordero, F.; Lin, S.; Banaszynski, L.A.; Garcia, B.A.; Muir, T.W.; Becher, O.J.; Allis, C.D. Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science,  2013, 340(6134), 857-861.
 [http://dx.doi.org/10.1126/science.1232245] [PMID:  23539183]

[197]
Viré, E.; Brenner, C.; Deplus, R.; Blanchon, L.; Fraga, M.; Didelot, C.; Morey, L.; Van Eynde, A.; Bernard, D.; Vanderwinden, J.M.; Bollen, M.; Esteller, M.; Di Croce, L.; de Launoit, Y.; Fuks, F. The Polycomb group protein EZH2 directly controls DNA methylation. Nature,  2006, 439(7078), 871-874.
 [http://dx.doi.org/10.1038/nature04431] [PMID:  16357870]

[198]
Zheng, S.; Houseman, E.A.; Morrison, Z.; Wrensch, M.R.; Patoka, J.S.; Ramos, C.; Haas-Kogan, D.A.; McBride, S.; Marsit, C.J.; Christensen, B.C.; Nelson, H.H.; Stokoe, D.; Wiemels, J.L.; Chang, S.M.; Prados, M.D.; Tihan, T.; Vandenberg, S.R.; Kelsey, K.T.; Berger, M.S.; Wiencke, J.K. DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression. Neuro-oncol.,  2011, 13(3), 280-289.
 [http://dx.doi.org/10.1093/neuonc/noq190] [PMID:  21339190]

[199]
Lewis, P.W.; Allis, C.D. Poisoning the “histone code” in pediatric gliomagenesis. Cell Cycle,  2013, 12(20), 3241-3242.
 [http://dx.doi.org/10.4161/cc.26356] [PMID:  24036540]

[200]
Behjati, S.; Tarpey, P.S.; Presneau, N.; Scheipl, S.; Pillay, N.; Van Loo, P.; Wedge, D.C.; Cooke, S.L.; Gundem, G.; Davies, H.; Nik-Zainal, S.; Martin, S.; McLaren, S.; Goody, V.; Robinson, B.; Butler, A.; Teague, J.W.; Halai, D.; Khatri, B.; Myklebost, O.; Baumhoer, D.; Jundt, G.; Hamoudi, R.; Tirabosco, R.; Amary, M.F.; Futreal, P.A.; Stratton, M.R.; Campbell, P.J.; Flanagan, A.M. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat. Genet.,  2013, 45(12), 1479-1482.
 [http://dx.doi.org/10.1038/ng.2814] [PMID:  24162739]

[201]
Sturm, D.; Witt, H.; Hovestadt, V.; Khuong-Quang, D.A.; Jones, D.T.W.; Konermann, C.; Pfaff, E.; Tönjes, M.; Sill, M.; Bender, S.; Kool, M.; Zapatka, M.; Becker, N.; Zucknick, M.; Hielscher, T.; Liu, X.Y.; Fontebasso, A.M.; Ryzhova, M.; Albrecht, S.; Jacob, K.; Wolter, M.; Ebinger, M.; Schuhmann, M.U.; van Meter, T.; Frühwald, M.C.; Hauch, H.; Pekrun, A.; Radlwimmer, B.; Niehues, T.; von Komorowski, G.; Dürken, M.; Kulozik, A.E.; Madden, J.; Donson, A.; Foreman, N.K.; Drissi, R.; Fouladi, M.; Scheurlen, W.; von Deimling, A.; Monoranu, C.; Roggendorf, W.; Herold-Mende, C.; Unterberg, A.; Kramm, C.M.; Felsberg, J.; Hartmann, C.; Wiestler, B.; Wick, W.; Milde, T.; Witt, O.; Lindroth, A.M.; Schwartzentruber, J.; Faury, D.; Fleming, A.; Zakrzewska, M.; Liberski, P.P.; Zakrzewski, K.; Hauser, P.; Garami, M.; Klekner, A.; Bognar, L.; Morrissy, S.; Cavalli, F.; Taylor, M.D.; van Sluis, P.; Koster, J.; Versteeg, R.; Volckmann, R.; Mikkelsen, T.; Aldape, K.; Reifenberger, G.; Collins, V.P.; Majewski, J.; Korshunov, A.; Lichter, P.; Plass, C.; Jabado, N.; Pfister, S.M. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell,  2012, 22(4), 425-437.
 [http://dx.doi.org/10.1016/j.ccr.2012.08.024] [PMID:  23079654]

[202]
Schwartzentruber, J.; Korshunov, A.; Liu, X.Y.; Jones, D.T.W.; Pfaff, E.; Jacob, K.; Sturm, D.; Fontebasso, A.M.; Quang, D.A.K.; Tönjes, M.; Hovestadt, V.; Albrecht, S.; Kool, M.; Nantel, A.; Konermann, C.; Lindroth, A.; Jäger, N.; Rausch, T.; Ryzhova, M.; Korbel, J.O.; Hielscher, T.; Hauser, P.; Garami, M.; Klekner, A.; Bognar, L.; Ebinger, M.; Schuhmann, M.U.; Scheurlen, W.; Pekrun, A.; Frühwald, M.C.; Roggendorf, W.; Kramm, C.; Dürken, M.; Atkinson, J.; Lepage, P.; Montpetit, A.; Zakrzewska, M.; Zakrzewski, K.; Liberski, P.P.; Dong, Z.; Siegel, P.; Kulozik, A.E.; Zapatka, M.; Guha, A.; Malkin, D.; Felsberg, J.; Reifenberger, G.; von Deimling, A.; Ichimura, K.; Collins, V.P.; Witt, H.; Milde, T.; Witt, O.; Zhang, C.; Castelo-Branco, P.; Lichter, P.; Faury, D.; Tabori, U.; Plass, C.; Majewski, J.; Pfister, S.M.; Jabado, N. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature,  2012, 482(7384), 226-231.
 [http://dx.doi.org/10.1038/nature10833] [PMID:  22286061]

[203]
Lovejoy, C.A.; Li, W.; Reisenweber, S.; Thongthip, S.; Bruno, J.; de Lange, T.; De, S.; Petrini, J.H.J.; Sung, P.A.; Jasin, M.; Rosenbluh, J.; Zwang, Y.; Weir, B.A.; Hatton, C.; Ivanova, E.; Macconaill, L.; Hanna, M.; Hahn, W.C.; Lue, N.F.; Reddel, R.R.; Jiao, Y.; Kinzler, K.; Vogelstein, B.; Papadopoulos, N.; Meeker, A.K. Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway. PLoS Genet.,  2012, 8(7), e1002772.
 [http://dx.doi.org/10.1371/journal.pgen.1002772] [PMID:  22829774]

[204]
Marks, P.A.; Xu, W.S. Histone deacetylase inhibitors: Potential in cancer therapy. J. Cell. Biochem.,  2009, 107(4), 600-608.
 [http://dx.doi.org/10.1002/jcb.22185] [PMID:  19459166]

[205]
Yin, D.; Ong, J.M.; Hu, J.; Desmond, J.C.; Kawamata, N.; Konda, B.M.; Black, K.L.; Koeffler, H.P. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor: effects on gene expression and growth of glioma cells in vitro and in vivo. Clin. Cancer Res.,  2007, 13(3), 1045-1052.
 [http://dx.doi.org/10.1158/1078-0432.CCR-06-1261] [PMID:  17289901]

[206]
Fouladi, M.; Park, J.R.; Stewart, C.F.; Gilbertson, R.J.; Schaiquevich, P.; Sun, J.; Reid, J.M.; Ames, M.M.; Speights, R.; Ingle, A.M.; Zwiebel, J.; Blaney, S.M.; Adamson, P.C. Pediatric phase I trial and pharmacokinetic study of vorinostat: a Children’s Oncology Group phase I consortium report. J. Clin. Oncol.,  2010, 28(22), 3623-3629.
 [http://dx.doi.org/10.1200/JCO.2009.25.9119] [PMID:  20606092]

[207]
Spiller, S.E.; Ditzler, S.H.; Pullar, B.J.; Olson, J.M. Response of preclinical medulloblastoma models to combination therapy with 13-cis retinoic acid and suberoylanilide hydroxamic acid (SAHA). J. Neurooncol.,  2008, 87(2), 133-141.
 [http://dx.doi.org/10.1007/s11060-007-9505-1] [PMID:  18060600]

[208]
Furchert, S.E.; Lanvers-Kaminsky, C.; Juürgens, H.; Jung, M.; Loidl, A.; Frühwald, M.C. Inhibitors of histone deacetylases as potential therapeutic tools for high-risk embryonal tumors of the nervous system of childhood. Int. J. Cancer,  2007, 120(8), 1787-1794.
 [http://dx.doi.org/10.1002/ijc.22401] [PMID:  17230517]

[209]
Spiller, S.E.; Ravanpay, A.C.; Hahn, A.W.; Olson, J.M. Suberoylanilide hydroxamic acid is effective in preclinical studies of medulloblastoma. J. Neurooncol.,  2006, 79(3), 259-270.
 [http://dx.doi.org/10.1007/s11060-006-9142-0] [PMID:  16645722]

[210]
Masoudi, A.; Elopre, M.; Amini, E.; Nagel, M.E.; Ater, J.L.; Gopalakrishnan, V.; Wolff, J.E. Influence of valproic acid on outcome of high-grade gliomas in children. Anticancer Res.,  2008, 28(4C), 2437-2442.
 [PMID:  18751431]

[211]
Su, J.M.; Li, X.N.; Thompson, P.; Ou, C.N.; Ingle, A.M.; Russell, H.; Lau, C.C.; Adamson, P.C.; Blaney, S.M. Phase 1 study of valproic acid in pediatric patients with refractory solid or CNS tumors: a children’s oncology group report. Clin. Cancer Res.,  2011, 17(3), 589-597.
 [http://dx.doi.org/10.1158/1078-0432.CCR-10-0738] [PMID:  21115653]

[212]
Wolff, J.E.A.; Kramm, C.; Kortmann, R.D.; Pietsch, T.; Rutkowski, S.; Jorch, N.; Gnekow, A.; Driever, P.H. Valproic acid was well tolerated in heavily pretreated pediatric patients with high-grade glioma. J. Neurooncol.,  2008, 90(3), 309-314.
 [http://dx.doi.org/10.1007/s11060-008-9662-x] [PMID:  18679579]

[213]
Graham, C.; Tucker, C.; Creech, J.; Favours, E.; Billups, C.A.; Liu, T.; Fouladi, M.; Freeman, B.B., III; Stewart, C.F.; Houghton, P.J. Evaluation of the antitumor efficacy, pharmacokinetics, and pharmacodynamics of the histone deacetylase inhibitor depsipeptide in childhood cancer models in vivo. Clin. Cancer Res.,  2006, 12(1), 223-234.
 [http://dx.doi.org/10.1158/1078-0432.CCR-05-1225] [PMID:  16397046]

[214]
Iwamoto, F.M.; Lamborn, K.R.; Robins, H.I.; Mehta, M.P.; Chang, S.M.; Butowski, N.A.; DeAngelis, L.M.; Abrey, L.E.; Zhang, W.T.; Prados, M.D.; Fine, H.A. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro-oncol.,  2010, 12(8), 855-861.
 [http://dx.doi.org/10.1093/neuonc/noq025] [PMID:  20200024]

[215]
Hdeib, A.; Sloan, A.E. Convection-enhanced delivery of 131 I-chTNT-1/B mAB for treatment of high-grade adult gliomas. Expert Opin. Biol. Ther.,  2011, 11(6), 799-806.
 [http://dx.doi.org/10.1517/14712598.2011.579097] [PMID:  21521146]

[216]
Chilamakuri, R.; Agarwal, S.J.C. Dual Targeting of PI3K and HDAC by CUDC-907 inhibits pediatric neuroblastoma growth. Cancers (Basel),  2022, 14(4), 1067.
 [http://dx.doi.org/10.3390/cancers14041067]

[217]
Corrales-Medina, F.F.; Manton, C.A.; Orlowski, R.Z.; Chandra, J.J. Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models. Leuk. Res.,  2015, 39(3), 371-379.

[218]
Nagaraja, S.; Vitanza, N.A.; Woo, P.J.; Taylor, K.R.; Liu, F.; Zhang, L. Transcriptional dependencies in diffuse intrinsic pontine glioma. Cancer Cell,  2017, 31(5), 635-652.
 [http://dx.doi.org/10.1016/j.ccell.2017.03.011]

[219]
Knipstein, J.; Gore, L. Entinostat for treatment of solid tumors and hematologic malignancies. Expert Opin. Investig. Drugs,  2011, 20(10), 1455-1467.

[220]
Li, X-N.; Shu, Q.; Su, J.M-F.; Perlaky, L.; Blaney, S.M.; Lau, C.C.J. Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC. Mol. Cancer Ther.,  2005, 4(12), 1912-1922.

[221]
Engelhard, H.H.; Duncan, H.A.; Kim, S.; Criswell, P.S.; Van Eldik, L.J.N. Therapeutic effects of sodium butyrate on glioma cells in vitro and in the rat C6 glioma model. Neurosurgery,  2001, 48(3), 616-624.
 [http://dx.doi.org/10.1097/00006123-200103000-00035]

[222]
Rahman, R.; Osteso-Ibanez, T.; Hirst, R.A.; Levesley, J.; Kilday, J-P.; Quinn, S. Histone deacetylase inhibition attenuates cell growth with associated telomerase inhibition in high-grade childhood brain tumor cells. Mol. Cancer Ther.,  2010, 9(9), 2568-2581.

[223]
Su, J.M.; Kilburn, L.B.; Mansur, D.B.; Krailo, M.; Buxton, A.; Adekunle, A.; Gajjar, A.; Adamson, P.C.; Weigel, B.; Fox, E.; Blaney, S.M.; Fouladi, M. Phase I/II trial of vorinostat and radiation and maintenance vorinostat in children with diffuse intrinsic pontine glioma: A Children’s Oncology Group report. Neuro-oncol.,  2022, 24(4), 655-664.
 [http://dx.doi.org/10.1093/neuonc/noab188] [PMID:  34347089]

[224]
Agarwal, N.; McPherson, J.P.; Bailey, H.; Gupta, S.; Werner, T.L.; Reddy, G.; Bhat, G.; Bailey, E.B.; Sharma, S. A phase I clinical trial of the effect of belinostat on the pharmacokinetics and pharmacodynamics of warfarin. Cancer Chemother. Pharmacol.,  2016, 77(2), 299-308.
 [http://dx.doi.org/10.1007/s00280-015-2934-1] [PMID:  26719074]

[225]
Algar, E.M.; Muscat, A.; Dagar, V.; Rickert, C.; Chow, C.W.; Biegel, J.A.; Ekert, P.G.; Saffery, R.; Craig, J.; Johnstone, R.W.; Ashley, D.M. Imprinted CDKN1C is a tumor suppressor in rhabdoid tumor and activated by restoration of SMARCB1 and histone deacetylase inhibitors. PLoS One,  2009, 4(2), e4482.
 [http://dx.doi.org/10.1371/journal.pone.0004482] [PMID:  19221586]

[226]
Nimmervoll, B.V.; Boulos, N.; Bianski, B.; Dapper, J.; DeCuypere, M.; Shelat, A. Establishing a preclinical multidisciplinary board for brain tumors. Clin. Cancer Res.,  2018, 24(7), 1654-1666.

[227]
Northcott, P.A.; Jones, D.T.; Kool, M.; Robinson, G.W.; Gilbertson, R.J.; Cho, Y-J. Medulloblastomics: The end of the beginning. Nat. Rev. Cancer,  2012, 12(12), 818-834.
 [http://dx.doi.org/10.1038/nrc3410]

[228]
Alexander, B.M.; Ba, S.; Berger, M.S.; Berry, D.A.; Cavenee, W.K.; Chang, S.M.; Cloughesy, T.F.; Jiang, T.; Khasraw, M.; Li, W.; Mittman, R.; Poste, G.H.; Wen, P.Y.; Yung, W.K.A.; Barker, A.D. Adaptive global innovative learning environment for glioblastoma: GBM AGILE. Clin. Cancer Res.,  2018, 24(4), 737-743.
 [http://dx.doi.org/10.1158/1078-0432.CCR-17-0764] [PMID:  28814435]

[229]
Chow, S-C. Adaptive clinical trial design. Annu. Rev. Med.,  2017, 65, 405-415.

[230]
Hargrave, D.R.; Bouffet, E.; Tabori, U.; Broniscer, A.; Cohen, K.J.; Hansford, J.R.; Geoerger, B.; Hingorani, P.; Dunkel, I.J.; Russo, M.W.; Tseng, L.; Dasgupta, K.; Gasal, E.; Whitlock, J.A.; Kieran, M.W. Efficacy and safety of dabrafenib in pediatric patients with BRAF V600 mutation-positive relapsed or refractory low-grade Glioma: Results from a phase I/IIa study. Clin. Cancer Res.,  2019, 25(24), 7303-7311.
 [http://dx.doi.org/10.1158/1078-0432.CCR-19-2177] [PMID:  31811016]

[231]
Nicolaides, T.; Nazemi, K.; Crawford, J.; Kilburn, L.; Minturn, J.; Gajjar, A.; Gauvain, K.; Leary, S.; Dhall, G.; Aboian, M.; Robinson, G.; Molinaro, A.; Mueller, S.; Prados, M. Pdct-19. A safety study of vemurafenib, an oral inhibitor of braf(V600e), in children with recurrent/refractory braf(V600e) mutant brain tumors: Pnoc-002. Neuro-oncol.,  2017, 19(Suppl. 6), vi188.
 [http://dx.doi.org/10.1093/neuonc/nox168.761]

[232]
Dobbins, R.; MacDonald, T.J.; Munn, D.H.; Johnson, T.S. Pediatric trial of indoximod with chemotherapy and radiation for relapsed brain tumors or newly diagnosed DIPG.,  , NCT04049669.

[233]
Kramer, B.; Singh, R.; Wischusen, J.; Dent, R.; Rush, A.; Middlemiss, S.; Ching, Y.W.; Alexander, I.E.; McCowage, G. Clinical Trial of MGMT (P140K). Hum. Gene Ther.,  2018, 29(8), 874-885.
 [http://dx.doi.org/10.1089/hum.2017.235] [PMID:  29385852]

[234]
Parasramka, S.; Talari, G.; Rosenfeld, M.; Guo, J. Procarbazine, lomustine and vincristine for recurrent high-grade glioma. Cochrane Database Syst. Rev.,  2017, 7(7), CD011773.

[235]
Dunsmore, K.P.; Winter, S.; Devidas, M.; Wood, B.L.; Esiashvili, N.; Eisenberg, N. COG AALL0434: A randomized trial testing nelarabine in newly diagnosed t-cell malignancy. J. Clin. Oncol.,  2018, 36(15), 10500.

[236]
Stein, A.; Franklin, J.L.; Chia, V.M.; Arrindell, D.; Kormany, W.; Wright, J. Benefit-risk assessment of blinatumomab in the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Drug Saf.,  2019, 42(5), 587-601.

[237]
Amin, N.L. Osteonecrosis and bone health in children, teenagers and young people with leukaemia. PhD thesis, University of Leeds., 2019.

[238]
Blaney, S.M.; Boyett, J.; Friedman, H.; Gajjar, A.; Geyer, R.; Horowtiz, M.; Hunt, D.; Kieran, M.; Kun, L.; Packer, R.; Phillips, P.; Pollack, I.F.; Prados, M.; Heideman, R. Phase I clinical trial of mafosfamide in infants and children aged 3 years or younger with newly diagnosed embryonal tumors: a pediatric brain tumor consortium study (PBTC-001). J. Clin. Oncol.,  2005, 23(3), 525-531.
 [http://dx.doi.org/10.1200/JCO.2005.06.544] [PMID:  15659498]

[239]
Doz, F.; Locatelli, F.; Baruchel, A.; Blin, N.; De Moerloose, B.; Frappaz, D. Phase I dose-escalation study of volasertib in pediatric patients with acute leukemia or advanced solid tumors. Pediatr. Blood Cancer,  2019, 66(10), e27900.
 [http://dx.doi.org/10.1002/pbc.27900]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1570159X21666230809110444	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

Targeting Histone 3 Variants Epigenetic Landscape and Inhibitory Immune Checkpoints: An Option for Paediatric Brain Tumours Therapy

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
