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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

Immune Checkpoint Inhibitors: Basics and Challenges

Author(s): Bin Li*, Ho Lam Chan and Pingping Chen*

Volume 26, Issue 17, 2019

Page: [3009 - 3025] Pages: 17

DOI: 10.2174/0929867324666170804143706

Price: $65

Abstract

Cancer is one of the most deadly diseases in the modern world. The last decade has witnessed dramatic advances in cancer treatment through immunotherapy. One extremely promising means to achieve anti-cancer immunity is to block the immune checkpoint pathways – mechanisms adopted by cancer cells to disguise themselves as regular components of the human body. Many review articles have described a variety of agents that are currently under extensive clinical evaluation. However, while checkpoint blockade is universally effective against a broad spectrum of cancer types and is mostly unrestricted by the mutation status of certain genes, only a minority of patients achieve a complete response. In this review, we summarize the basic principles of immune checkpoint inhibitors in both antibody and smallmolecule forms and also discuss potential mechanisms of resistance, which may shed light on further investigation to achieve higher clinical efficacy for these inhibitors.

Keywords: Immunotherapy, checkpoint blockade, T cells, CTLA-4, PD-1, resistance.

« Previous Next »
[1]
Chabner, B.A.; Roberts, T.G., Jr Timeline: Chemotherapy and the war on cancer. Nat. Rev. Cancer, 2005, 5(1), 65-72.
[http://dx.doi.org/10.1038/nrc1529] [PMID: 15630416]
[2]
Malet-Martino, M.; Martino, R. Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. Oncologist, 2002, 7(4), 288-323.
[http://dx.doi.org/10.1634/theoncologist.7-4-288] [PMID: 12185293]
[3]
Thomas, A.; Liu, S.V.; Subramaniam, D.S.; Giaccone, G. Refining the treatment of NSCLC according to histological and molecular subtypes. Nat. Rev. Clin. Oncol., 2015, 12(9), 511-526.
[http://dx.doi.org/10.1038/nrclinonc.2015.90] [PMID: 25963091]
[4]
Zhang, J.; Yang, P.L.; Gray, N.S. Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer, 2009, 9(1), 28-39.
[http://dx.doi.org/10.1038/nrc2559] [PMID: 19104514]
[5]
Barouch-Bentov, R.; Sauer, K. Mechanisms of drug resistance in kinases. Expert Opin. Investig. Drugs, 2011, 20(2), 153-208.
[http://dx.doi.org/10.1517/13543784.2011.546344] [PMID: 21235428]
[6]
SH, G. Efficacy of nivolumab in patients with previously traeted ad-vanced non-small cell lung cancer: subpopulation response analysis in a phase I trial. Presentation: IASLC 15th World Conference on Lung Can-cer, Sydney, Australia, 2013.
[7]
Schadendorf, D.; Hodi, F.S.; Robert, C.; Weber, J.S.; Margolin, K.; Hamid, O.; Patt, D.; Chen, T.T.; Berman, D.M.; Wolchok, J.D. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J. Clin. Oncol., 2015, 33(17), 1889-1894.
[http://dx.doi.org/10.1200/JCO.2014.56.2736] [PMID: 25667295]
[8]
Lebbé, C.; Weber, J.S.; Maio, M.; Neyns, B.; Harmankaya, K.; Hamid, O.; O’Day, S.J.; Konto, C.; Cykowski, L.; McHenry, M.B.; Wolchok, J.D. Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies. Ann. Oncol., 2014, 25(11), 2277-2284.
[http://dx.doi.org/10.1093/annonc/mdu441] [PMID: 25210016]
[9]
McCarthy, E.F. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop. J., 2006, 26, 154-158.
[PMID: 16789469]
[10]
Hollinshead, A.C.; Stewart, T.H. Specific and nonspecific immunotherapy as an adjunct to curative surgery for cancer of the lung. Yale J. Biol. Med., 1981, 54(5), 367-379.
[PMID: 7039148]
[11]
Rosenberg, S.A.; Restifo, N.P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science, 2015, 348(6230), 62-68.
[http://dx.doi.org/10.1126/science.aaa4967] [PMID: 25838374]
[12]
Guo, C.; Manjili, M.H.; Subjeck, J.R.; Sarkar, D.; Fisher, P.B.; Wang, X.Y. Therapeutic cancer vaccines: past, present, and future. Adv. Cancer Res., 2013, 119, 421-475.
[http://dx.doi.org/10.1016/B978-0-12-407190-2.00007-1] [PMID: 23870514]
[13]
Gajewski, T.F.; Schreiber, H.; Fu, Y.X. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol., 2013, 14(10), 1014-1022.
[http://dx.doi.org/10.1038/ni.2703] [PMID: 24048123]
[14]
Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, 12(4), 252-264.
[http://dx.doi.org/10.1038/nrc3239] [PMID: 22437870]
[15]
Rivoltini, L.; Carrabba, M.; Huber, V.; Castelli, C.; Novellino, L.; Dalerba, P.; Mortarini, R.; Arancia, G.; Anichini, A.; Fais, S.; Parmiani, G. Immunity to cancer: attack and escape in T lymphocyte-tumor cell interaction. Immunol. Rev., 2002, 188, 97-113.
[http://dx.doi.org/10.1034/j.1600-065X.2002.18809.x] [PMID: 12445284]
[16]
Renkvist, N.; Castelli, C.; Robbins, P.F.; Parmiani, G. A listing of human tumor antigens recognized by T cells. Cancer Immunol. Immunother., 2001, 50(1), 3-15.
[http://dx.doi.org/10.1007/s002620000169] [PMID: 11315507]
[17]
Lipson, E.J.; Drake, C.G. Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Clin. Cancer Res., 2011, 17(22), 6958-6962.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1595] [PMID: 21900389]
[18]
Paddock, L.E.; Lu, S.E.; Bandera, E.V.; Rhoads, G.G.; Fine, J.; Paine, S.; Barnhill, R.; Berwick, M. Skin self-examination and long-term melanoma survival. Melanoma Res., 2016, 26(4), 401-408.
[http://dx.doi.org/10.1097/CMR.0000000000000255] [PMID: 26990272]
[19]
Sharon, E.; Streicher, H.; Goncalves, P.; Chen, H.X. Immune checkpoint inhibitors in clinical trials. Chin. J. Cancer, 2014, 33(9), 434-444.
[http://dx.doi.org/10.5732/cjc.014.10122] [PMID: 25189716]
[20]
Hanaizi, Z.; van Zwieten-Boot, B.; Calvo, G.; Lopez, A.S.; van Dartel, M.; Camarero, J.; Abadie, E.; Pignatti, F. The European Medicines Agency review of ipilimumab (Yervoy) for the treatment of advanced (unresectable or metastatic) melanoma in adults who have received prior therapy: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. Eur. J. Cancer, 2012, 48(2), 237-242.
[http://dx.doi.org/10.1016/j.ejca.2011.09.018] [PMID: 22030452]
[21]
Dariavach, P.; Mattéi, M.G.; Golstein, P.; Lefranc, M.P. Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. Eur. J. Immunol., 1988, 18(12), 1901-1905.
[http://dx.doi.org/10.1002/eji.1830181206] [PMID: 3220103]
[22]
Walunas, T.L.; Lenschow, D.J.; Bakker, C.Y.; Linsley, P.S.; Freeman, G.J.; Green, J.M.; Thompson, C.B.; Bluestone, J.A. CTLA-4 can function as a negative regulator of T cell activation. Immunity, 1994, 1(5), 405-413.
[http://dx.doi.org/10.1016/1074-7613(94)90071-X] [PMID: 7882171]
[23]
Krummel, M.F.; Allison, J.P. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med., 1995, 182(2), 459-465.
[http://dx.doi.org/10.1084/jem.182.2.459] [PMID: 7543139]
[24]
Linsley, P.S.; Greene, J.L.; Tan, P.; Bradshaw, J.; Ledbetter, J.A.; Anasetti, C.; Damle, N.K. Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J. Exp. Med., 1992, 176(6), 1595-1604.
[http://dx.doi.org/10.1084/jem.176.6.1595] [PMID: 1334116]
[25]
Kearney, E.R.; Walunas, T.L.; Karr, R.W.; Morton, P.A.; Loh, D.Y.; Bluestone, J.A.; Jenkins, M.K. Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4. J. Immunol., 1995, 155(3), 1032-1036.
[PMID: 7543510]
[26]
Hodi, F.S.; O’Day, S.J.; McDermott, D.F.; Weber, R.W.; Sosman, J.A.; Haanen, J.B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J.C.; Akerley, W.; van den Eertwegh, A.J.; Lutzky, J.; Lorigan, P.; Vaubel, J.M.; Linette, G.P.; Hogg, D.; Ottensmeier, C.H.; Lebbé, C.; Peschel, C.; Quirt, I.; Clark, J.I.; Wolchok, J.D.; Weber, J.S.; Tian, J.; Yellin, M.J.; Nichol, G.M.; Hoos, A.; Urba, W.J. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med., 2010, 363(8), 711-723.
[http://dx.doi.org/10.1056/NEJMoa1003466] [PMID: 20525992]
[27]
Jemal, A.; Siegel, R.; Xu, J.; Ward, E. Cancer statistics, 2010. CA Cancer J. Clin., 2010, 60(5), 277-300.
[http://dx.doi.org/10.3322/caac.20073] [PMID: 20610543]
[28]
Lenschow, D.J.; Walunas, T.L.; Bluestone, J.A. CD28/B7 system of T cell costimulation. Annu. Rev. Immunol., 1996, 14, 233-258.
[http://dx.doi.org/10.1146/annurev.immunol.14.1.233] [PMID: 8717514]
[29]
Harris, N.L.; Ronchese, F. The role of B7 costimulation in T-cell immunity. Immunol. Cell Biol., 1999, 77(4), 304-311.
[http://dx.doi.org/10.1046/j.1440-1711.1999.00835.x] [PMID: 10457196]
[30]
Riley, J.L.; Mao, M.; Kobayashi, S.; Biery, M.; Burchard, J.; Cavet, G.; Gregson, B.P.; June, C.H.; Linsley, P.S. Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc. Natl. Acad. Sci. USA, 2002, 99(18), 11790-11795.
[http://dx.doi.org/10.1073/pnas.162359999] [PMID: 12195015]
[31]
Schneider, H.; Downey, J.; Smith, A.; Zinselmeyer, B.H.; Rush, C.; Brewer, J.M.; Wei, B.; Hogg, N.; Garside, P.; Rudd, C.E. Reversal of the TCR stop signal by CTLA-4. Science, 2006, 313(5795), 1972-1975.
[http://dx.doi.org/10.1126/science.1131078] [PMID: 16931720]
[32]
Egen, J.G.; Allison, J.P. Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity, 2002, 16(1), 23-35.
[http://dx.doi.org/10.1016/S1074-7613(01)00259-X] [PMID: 11825563]
[33]
Parry, R.V.; Chemnitz, J.M.; Frauwirth, K.A.; Lanfranco, A.R.; Braunstein, I.; Kobayashi, S.V.; Linsley, P.S.; Thompson, C.B.; Riley, J.L. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell. Biol., 2005, 25(21), 9543-9553.
[http://dx.doi.org/10.1128/MCB.25.21.9543-9553.2005] [PMID: 16227604]
[34]
Schneider, H.; Mandelbrot, D.A.; Greenwald, R.J.; Ng, F.; Lechler, R.; Sharpe, A.H.; Rudd, C.E. Cutting edge: CTLA-4 (CD152) differentially regulates mitogen-activated protein kinases (extracellular signal-regulated kinase and c-Jun N-terminal kinase) in CD4+ T cells from receptor/ligand-deficient mice. J. Immunol., 2002, 169(7), 3475-3479.
[http://dx.doi.org/10.4049/jimmunol.169.7.3475] [PMID: 12244135]
[35]
Linsley, P.S.; Greene, J.L.; Brady, W.; Bajorath, J.; Ledbetter, J.A.; Peach, R. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity, 1994, 1(9), 793-801.
[http://dx.doi.org/10.1016/S1074-7613(94)80021-9] [PMID: 7534620]
[36]
Sansom, D.M. CD28, CTLA-4 and their ligands: who does what and to whom? Immunology, 2000, 101(2), 169-177.
[http://dx.doi.org/10.1046/j.1365-2567.2000.00121.x] [PMID: 11012769]
[37]
Phan, G.Q.; Yang, J.C.; Sherry, R.M.; Hwu, P.; Topalian, S.L.; Schwartzentruber, D.J.; Restifo, N.P.; Haworth, L.R.; Seipp, C.A.; Freezer, L.J.; Morton, K.E.; Mavroukakis, S.A.; Duray, P.H.; Steinberg, S.M.; Allison, J.P.; Davis, T.A.; Rosenberg, S.A. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl. Acad. Sci. USA, 2003, 100(14), 8372-8377.
[http://dx.doi.org/10.1073/pnas.1533209100] [PMID: 12826605]
[38]
Tivol, E.A.; Borriello, F.; Schweitzer, A.N.; Lynch, W.P.; Bluestone, J.A.; Sharpe, A.H. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity, 1995, 3(5), 541-547.
[http://dx.doi.org/10.1016/1074-7613(95)90125-6] [PMID: 7584144]
[39]
Waterhouse, P.; Penninger, J.M.; Timms, E.; Wakeham, A.; Shahinian, A.; Lee, K.P.; Thompson, C.B.; Griesser, H.; Mak, T.W. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science, 1995, 270(5238), 985-988.
[http://dx.doi.org/10.1126/science.270.5238.985] [PMID: 7481803]
[40]
Seliger, B. Expression and function of CTLA4 in melanoma. ASCO Annual meeting, 2013.
[41]
Hoos, A. Development of immuno-oncology drugs - from CTLA4 to PD1 to the next generations. Nat. Rev. Drug Discov., 2016, 15(4), 235-247.
[http://dx.doi.org/10.1038/nrd.2015.35] [PMID: 26965203]
[42]
Zou, W.; Wolchok, J.D.; Chen, L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci. Transl. Med., 2016, 8(328), 328rv4.
[http://dx.doi.org/10.1126/scitranslmed.aad7118] [PMID: 26936508]
[43]
Agata, Y.; Kawasaki, A.; Nishimura, H.; Ishida, Y.; Tsubata, T.; Yagita, H.; Honjo, T. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int. Immunol., 1996, 8(5), 765-772.
[http://dx.doi.org/10.1093/intimm/8.5.765] [PMID: 8671665]
[44]
Albiges, L.; Fay, A.P.; Xie, W.; Krajewski, K.; McDermott, D.F.; Heng, D.Y.; Dariane, C.; DeVelasco, G.; Lester, R.; Escudier, B.; Choueiri, T.K. Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma. Eur. J. Cancer, 2015, 51(17), 2580-2586.
[http://dx.doi.org/10.1016/j.ejca.2015.08.017] [PMID: 26346135]
[45]
Hematology/Oncology (Cancer) Approvals & Safety Notifications; FDA Web site, 2015.Available at. https://www.fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications [Updated April 24].
[46]
Kazandjian, D.; Suzman, D.L.; Blumenthal, G.; Mushti, S.; He, K.; Libeg, M.; Keegan, P.; Pazdur, R. FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Oncologist, 2016, 21(5), 634-642.
[http://dx.doi.org/10.1634/theoncologist.2015-0507] [PMID: 26984449]
[47]
Torre, L.A.; Siegel, R.L.; Jemal, A. Lung cancer statistics. Adv. Exp. Med. Biol., 2016, 893, 1-19.
[http://dx.doi.org/10.1007/978-3-319-24223-1_1] [PMID: 26667336]
[48]
Gandini, S.; Massi, D.; Mandalà, M. PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. Crit. Rev. Oncol. Hematol., 2016, 100, 88-98.
[http://dx.doi.org/10.1016/j.critrevonc.2016.02.001] [PMID: 26895815]
[49]
Ishida, Y.; Agata, Y.; Shibahara, K.; Honjo, T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J., 1992, 11(11), 3887-3895.
[http://dx.doi.org/10.1002/j.1460-2075.1992.tb05481.x] [PMID: 1396582]
[50]
Dong, H.; Zhu, G.; Tamada, K.; Flies, D.B.; van Deursen, J.M.; Chen, L. B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity, 2004, 20(3), 327-336.
[http://dx.doi.org/10.1016/S1074-7613(04)00050-0] [PMID: 15030776]
[51]
Gros, A.; Robbins, P.F.; Yao, X.; Li, Y.F.; Turcotte, S.; Tran, E.; Wunderlich, J.R.; Mixon, A.; Farid, S.; Dudley, M.E.; Hanada, K.; Almeida, J.R.; Darko, S.; Douek, D.C.; Yang, J.C.; Rosenberg, S.A. PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors. J. Clin. Invest., 2014, 124(5), 2246-2259.
[http://dx.doi.org/10.1172/JCI73639] [PMID: 24667641]
[52]
Thibult, M.L.; Mamessier, E.; Gertner-Dardenne, J.; Pastor, S.; Just-Landi, S.; Xerri, L.; Chetaille, B.; Olive, D. PD-1 is a novel regulator of human B-cell activation. Int. Immunol., 2013, 25(2), 129-137.
[http://dx.doi.org/10.1093/intimm/dxs098] [PMID: 23087177]
[53]
Norris, S.; Coleman, A.; Kuri-Cervantes, L.; Bower, M.; Nelson, M.; Goodier, M.R. PD-1 expression on natural killer cells and CD8(+) T cells during chronic HIV-1 infection. Viral Immunol., 2012, 25(4), 329-332.
[http://dx.doi.org/10.1089/vim.2011.0096] [PMID: 22742708]
[54]
Lim, T.S.; Chew, V.; Sieow, J.L.; Goh, S.; Yeong, J.P.; Soon, A.L.; Ricciardi-Castagnoli, P. PD-1 expression on dendritic cells suppresses CD8+ T cell function and antitumor immunity. OncoImmunology, 2015, 5(3), e1085146.
[http://dx.doi.org/10.1080/2162402X.2015.1085146] [PMID: 27141339]
[55]
Dong, H.; Zhu, G.; Tamada, K.; Chen, L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med., 1999, 5(12), 1365-1369.
[http://dx.doi.org/10.1038/70932] [PMID: 10581077]
[56]
Nishimura, H.; Minato, N.; Nakano, T.; Honjo, T. Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int. Immunol., 1998, 10(10), 1563-1572.
[http://dx.doi.org/10.1093/intimm/10.10.1563] [PMID: 9796923]
[57]
Latchman, Y.E.; Liang, S.C.; Wu, Y.; Chernova, T.; Sobel, R.A.; Klemm, M.; Kuchroo, V.K.; Freeman, G.J.; Sharpe, A.H. PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells. Proc. Natl. Acad. Sci. USA, 2004, 101(29), 10691-10696.
[http://dx.doi.org/10.1073/pnas.0307252101] [PMID: 15249675]
[58]
Freeman, G.J.; Long, A.J.; Iwai, Y.; Bourque, K.; Chernova, T.; Nishimura, H.; Fitz, L.J.; Malenkovich, N.; Okazaki, T.; Byrne, M.C.; Horton, H.F.; Fouser, L.; Carter, L.; Ling, V.; Bowman, M.R.; Carreno, B.M.; Collins, M.; Wood, C.R.; Honjo, T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med., 2000, 192(7), 1027-1034.
[http://dx.doi.org/10.1084/jem.192.7.1027] [PMID: 11015443]
[59]
Zou, W.; Chen, L. Inhibitory B7-family molecules in the tumour microenvironment. Nat. Rev. Immunol., 2008, 8(6), 467-477.
[http://dx.doi.org/10.1038/nri2326] [PMID: 18500231]
[60]
Butte, M.J.; Keir, M.E.; Phamduy, T.B.; Sharpe, A.H.; Freeman, G.J. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity, 2007, 27(1), 111-122.
[http://dx.doi.org/10.1016/j.immuni.2007.05.016] [PMID: 17629517]
[61]
Korman, A.J.; Peggs, K.S.; Allison, J.P. Checkpoint blockade in cancer immunotherapy. Adv. Immunol., 2006, 90, 297-339.
[http://dx.doi.org/10.1016/S0065-2776(06)90008-X] [PMID: 16730267]
[62]
Dong, H.; Strome, S.E.; Matteson, E.L.; Moder, K.G.; Flies, D.B.; Zhu, G.; Tamura, H.; Driscoll, C.L.; Chen, L. Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. J. Clin. Invest., 2003, 111(3), 363-370.
[http://dx.doi.org/10.1172/JCI16015] [PMID: 12569162]
[63]
Azuma, T.; Yao, S.; Zhu, G.; Flies, A.S.; Flies, S.J.; Chen, L. B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells. Blood, 2008, 111(7), 3635-3643.
[http://dx.doi.org/10.1182/blood-2007-11-123141] [PMID: 18223165]
[64]
Wang, S.; Bajorath, J.; Flies, D.B.; Dong, H.; Honjo, T.; Chen, L. Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction. J. Exp. Med., 2003, 197(9), 1083-1091.
[http://dx.doi.org/10.1084/jem.20021752] [PMID: 12719480]
[65]
Xiao, Y.; Yu, S.; Zhu, B.; Bedoret, D.; Bu, X.; Francisco, L.M.; Hua, P.; Duke-Cohan, J.S.; Umetsu, D.T.; Sharpe, A.H.; DeKruyff, R.H.; Freeman, G.J. RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J. Exp. Med., 2014, 211(5), 943-959.
[http://dx.doi.org/10.1084/jem.20130790] [PMID: 24752301]
[66]
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]
[67]
Redman, J.M.; Gibney, G.T.; Atkins, M.B. Advances in immunotherapy for melanoma. BMC Med., 2016, 14, 20.
[http://dx.doi.org/10.1186/s12916-016-0571-0] [PMID: 26850630]
[68]
Rosenberg, S.A. Decade in review-cancer immunotherapy: entering the mainstream of cancer treatment. Nat. Rev. Clin. Oncol., 2014, 11(11), 630-632.
[http://dx.doi.org/10.1038/nrclinonc.2014.174] [PMID: 25311350]
[69]
Walker, L.S. Treg and CTLA-4: two intertwining pathways to immune tolerance. J. Autoimmun., 2013, 45, 49-57.
[http://dx.doi.org/10.1016/j.jaut.2013.06.006] [PMID: 23849743]
[70]
McCoy, K.D.; Le Gros, G. The role of CTLA-4 in the regulation of T cell immune responses. Immunol. Cell Biol., 1999, 77(1), 1-10.
[http://dx.doi.org/10.1046/j.1440-1711.1999.00795.x] [PMID: 10101680]
[71]
Zou, W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat. Rev. Cancer, 2005, 5(4), 263-274.
[http://dx.doi.org/10.1038/nrc1586] [PMID: 15776005]
[72]
Naidoo, J.; Page, D.B.; Li, B.T.; Connell, L.C.; Schindler, K.; Lacouture, M.E.; Postow, M.A.; Wolchok, J.D. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann. Oncol., 2015, 26(12), 2375-2391.
[PMID: 26371282]
[73]
Weber, J.S.; Dummer, R.; de Pril, V.; Lebbé, C.; Hodi, F.S.; Investigators, M.D.X. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer, 2013, 119(9), 1675-1682.
[http://dx.doi.org/10.1002/cncr.27969] [PMID: 23400564]
[74]
Chow, L.Q. Exploring novel immune-related toxicities and endpoints with immune-checkpoint inhibitors in non-small cell lung cancer. Am. Soc. Clin. Oncol. Educ. Book, 2013.
[http://dx.doi.org/10.1200/EdBook_AM.2013.33.e280] [PMID: 23714523]
[75]
Callahan, M.K.; Postow, M.A.; Wolchok, J.D. CTLA-4 and PD-1 pathway blockade: combinations in the clinic. Front. Oncol., 2015, 4, 385.
[http://dx.doi.org/10.3389/fonc.2014.00385] [PMID: 25642417]
[76]
Watson, H.A.; Wehenkel, S.; Matthews, J.; Ager, A. SHP-1: the next checkpoint target for cancer immunotherapy? Biochem. Soc. Trans., 2016, 44(2), 356-362.
[http://dx.doi.org/10.1042/BST20150251] [PMID: 27068940]
[77]
Sheppard, K.A.; Fitz, L.J.; Lee, J.M.; Benander, C.; George, J.A.; Wooters, J.; Qiu, Y.; Jussif, J.M.; Carter, L.L.; Wood, C.R.; Chaudhary, D. PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta. FEBS Lett., 2004, 574(1-3), 37-41.
[http://dx.doi.org/10.1016/j.febslet.2004.07.083] [PMID: 15358536]
[78]
Chemnitz, J.M.; Parry, R.V.; Nichols, K.E.; June, C.H.; Riley, J.L. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J. Immunol., 2004, 173(2), 945-954.
[http://dx.doi.org/10.4049/jimmunol.173.2.945] [PMID: 15240681]
[79]
Yi, T.; Pathak, M.K.; Lindner, D.J.; Ketterer, M.E.; Farver, C.; Borden, E.C. Anticancer activity of sodium stibogluconate in synergy with IFNs. J. Immunol., 2002, 169(10), 5978-5985.
[http://dx.doi.org/10.4049/jimmunol.169.10.5978] [PMID: 12421984]
[80]
Kundu, S.; Fan, K.; Cao, M.; Lindner, D.J.; Zhao, Z.J.; Borden, E.; Yi, T. Novel SHP-1 inhibitors tyrosine phosphatase inhibitor-1 and analogs with preclinical anti-tumor activities as tolerated oral agents. J. Immunol., 2010, 184(11), 6529-6536.
[http://dx.doi.org/10.4049/jimmunol.0903562] [PMID: 20421638]
[81]
Chen, L.; Sung, S.S.; Yip, M.L.; Lawrence, H.R.; Ren, Y.; Guida, W.C.; Sebti, S.M.; Lawrence, N.J.; Wu, J. Discovery of a novel shp2 protein tyrosine phosphatase inhibitor. Mol. Pharmacol., 2006, 70(2), 562-570.
[http://dx.doi.org/10.1124/mol.106.025536] [PMID: 16717135]
[82]
Naing, A.; Reuben, J.M.; Camacho, L.H.; Gao, H.; Lee, B.N.; Cohen, E.N.; Verschraegen, C.; Stephen, S.; Aaron, J.; Hong, D.; Wheler, J.; Kurzrock, R.; Phase, I.; Phase, I. Dose escalation study of sodium stibogluconate (SSG), a protein tyrosine phosphatase inhibitor, combined with interferon alpha for patients with solid tumors. J. Cancer, 2011, 2, 81-89.
[http://dx.doi.org/10.7150/jca.2.81] [PMID: 21326629]
[83]
Sun, T.W.; Gao, Q.; Qiu, S.J.; Zhou, J.; Wang, X.Y.; Yi, Y.; Shi, J.Y.; Xu, Y.F.; Shi, Y.H.; Song, K.; Xiao, Y.S.; Fan, J. B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence. Cancer Immunol. Immunother., 2012, 61(11), 2171-2182.
[http://dx.doi.org/10.1007/s00262-012-1278-5] [PMID: 22729558]
[84]
Yamato, I.; Sho, M.; Nomi, T.; Akahori, T.; Shimada, K.; Hotta, K.; Kanehiro, H.; Konishi, N.; Yagita, H.; Nakajima, Y. Clinical importance of B7-H3 expression in human pancreatic cancer. Br. J. Cancer, 2009, 101(10), 1709-1716.
[http://dx.doi.org/10.1038/sj.bjc.6605375] [PMID: 19844235]
[85]
Nagase-Zembutsu, A.; Hirotani, K.; Yamato, M.; Yamaguchi, J.; Takata, T.; Yoshida, M.; Fukuchi, K.; Yazawa, M.; Takahashi, S.; Agatsuma, T. Development of DS-5573a: A novel afucosylated mAb directed at B7-H3 with potent antitumor activity. Cancer Sci., 2016, 107(5), 674-681.
[http://dx.doi.org/10.1111/cas.12915] [PMID: 26914241]
[86]
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. 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]
[87]
Leone, R.D.; Lo, Y.C.; Powell, J.D. A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy. Comput. Struct. Biotechnol. J., 2015, 13, 265-272.
[http://dx.doi.org/10.1016/j.csbj.2015.03.008] [PMID: 25941561]
[88]
Buchan, S.; Manzo, T.; Flutter, B.; Rogel, A.; Edwards, N.; Zhang, L.; Sivakumaran, S.; Ghorashian, S.; Carpenter, B.; Bennett, C.; Freeman, G.J.; Sykes, M.; Croft, M.; Al-Shamkhani, A.; Chakraverty, R. OX40- and CD27-mediated costimulation synergizes with anti-PD-L1 blockade by forcing exhausted CD8+ T cells to exit quiescence. J. Immunol., 2015, 194(1), 125-133.
[http://dx.doi.org/10.4049/jimmunol.1401644] [PMID: 25404365]
[89]
Foy, S.P.; Sennino, B.; dela Cruz, T.; Cote, J.J.; Gordon, E.J.; Kemp, F.; Xavier, V.; Franzusoff, A.; Rountree, R.B.; Mandl, S.J. Poxvirus-based active immunotherapy with PD-1 and LAG-3 dual immune checkpoint inhibition overcomes compensatory immune regulation, yielding complete tumor regression in mice. PLoS One, 2016, 11(2), e0150084.
[http://dx.doi.org/10.1371/journal.pone.0150084] [PMID: 26910562]
[90]
Ngiow, S.F.; Teng, M.W.; Smyth, M.J. Prospects for TIM3-targeted antitumor immunotherapy. Cancer Res., 2011, 71(21), 6567-6571.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1487] [PMID: 22009533]
[91]
NCT02413827. Available at. ClinicalTrials.gov, a service of the U.S. National Institutes of Health, 2016. [Updated 2016 July].
[92]
David, L.; Bajor, R.M.; Matthew, J. Riese; Lee, P. Richman; Xiaowei, Xu; Drew, A. Torigian; Erietta, Stelekati; Martha, Sweeney; Brendan, Sullivan; Lynn, M. Schuchter; Ravi, Amaravadi; E. John, Wherry; Robert, H. Vonderheide Combination of agonistic CD40 monoclonal antibody CP- 870,893 and anti-CTLA-4 antibody tremelimumab in patients with metastatic melanoma. American Association for Cancer Research Annual Meeting, 2015.
[93]
Eliopoulos, A.G.; Young, L.S. The role of the CD40 pathway in the pathogenesis and treatment of cancer. Curr. Opin. Pharmacol., 2004, 4(4), 360-367.
[http://dx.doi.org/10.1016/j.coph.2004.02.008] [PMID: 15251129]
[94]
van Kooten, C.; Banchereau, J. CD40-CD40 ligand. J. Leukoc. Biol., 2000, 67(1), 2-17.
[http://dx.doi.org/10.1002/jlb.67.1.2] [PMID: 10647992]
[95]
Johnson, P.; Challis, R.; Chowdhury, F.; Gao, Y.; Harvey, M.; Geldart, T.; Kerr, P.; Chan, C.; Smith, A.; Steven, N.; Edwards, C.; Ashton-Key, M.; Hodges, E.; Tutt, A.; Ottensmeier, C.; Glennie, M.; Williams, A. Clinical and biological effects of an agonist anti-CD40 antibody: a Cancer Research UK phase I study. Clin. Cancer Res., 2015, 21(6), 1321-1328.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2355] [PMID: 25589626]
[96]
Vonderheide, R.H.; Flaherty, K.T.; Khalil, M.; Stumacher, M.S.; Bajor, D.L.; Hutnick, N.A.; Sullivan, P.; Mahany, J.J.; Gallagher, M.; Kramer, A.; Green, S.J.; O’Dwyer, P.J.; Running, K.L.; Huhn, R.D.; Antonia, S.J. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J. Clin. Oncol., 2007, 25(7), 876-883.
[http://dx.doi.org/10.1200/JCO.2006.08.3311] [PMID: 17327609]
[97]
Lutz-Nicoladoni, C.; Wolf, D.; Sopper, S. Modulation of immune cell functions by the E3 ligase Cbl-b. Front. Oncol., 2015, 5, 58.
[http://dx.doi.org/10.3389/fonc.2015.00058] [PMID: 25815272]
[98]
Paolino, M.; Choidas, A.; Wallner, S.; Pranjic, B.; Uribesalgo, I.; Loeser, S.; Jamieson, A.M.; Langdon, W.Y.; Ikeda, F.; Fededa, J.P.; Cronin, S.J.; Nitsch, R.; Schultz-Fademrecht, C.; Eickhoff, J.; Menninger, S.; Unger, A.; Torka, R.; Gruber, T.; Hinterleitner, R.; Baier, G.; Wolf, D.; Ullrich, A.; Klebl, B.M.; Penninger, J.M. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature, 2014, 507(7493), 508-512.
[http://dx.doi.org/10.1038/nature12998] [PMID: 24553136]
[99]
Ebert, P.J.R.; Cheung, J.; Yang, Y.; McNamara, E.; Hong, R.; Moskalenko, M.; Gould, S.E.; Maecker, H.; Irving, B.A.; Kim, J.M.; Belvin, M.; Mellman, I. MAP kinase inhibition promotes T cell and anti-tumor activity in combination with PD-L1 checkpoint blockade. Immunity, 2016, 44(3), 609-621.
[http://dx.doi.org/10.1016/j.immuni.2016.01.024] [PMID: 26944201]
[100]
Paccez, J.D.; Vogelsang, M.; Parker, M.I.; Zerbini, L.F. The receptor tyrosine kinase Axl in cancer: biological functions and therapeutic implications. Int. J. Cancer, 2014, 134(5), 1024-1033.
[http://dx.doi.org/10.1002/ijc.28246] [PMID: 23649974]
[101]
Asiedu, M.K.; Beauchamp-Perez, F.D.; Ingle, J.N.; Behrens, M.D.; Radisky, D.C.; Knutson, K.L. AXL induces epithelial-to-mesenchymal transition and regulates the function of breast cancer stem cells. Oncogene, 2014, 33(10), 1316-1324.
[http://dx.doi.org/10.1038/onc.2013.57] [PMID: 23474758]
[102]
Terry, S.; Chouaib, S. EMT in immuno-resistance. Oncoscience, 2015, 2(10), 841-842.
[PMID: 26682272]
[103]
Gro Gausdal, K.D. Katarzyna, Wnuk-Lipinska; Kathleen, Wiertel; Monica, Hellesøy; Magnus, Blø; Lavina, Ahmed; Linn, Hodneland; Sergej, Kiprijanov; Rolf, A Brekken; James, B Lorens BGB324, a selective small molecule inhibitor of the receptor tyrosine kinase AXL, enhances immune checkpoint inhibitor efficacy. Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival, 2016.
[104]
Cicenas, J.; Kalyan, K.; Sorokinas, A.; Jatulyte, A.; Valiunas, D.; Kaupinis, A.; Valius, M. Highlights of the latest advances in research on CDK inhibitors. Cancers (Basel), 2014, 6(4), 2224-2242.
[http://dx.doi.org/10.3390/cancers6042224] [PMID: 25349887]
[105]
Dorand, R.D.; Nthale, J.; Myers, J.T.; Barkauskas, D.S.; Avril, S.; Chirieleison, S.M.; Pareek, T.K.; Abbott, D.W.; Stearns, D.S.; Letterio, J.J.; Huang, A.Y.; Petrosiute, A. Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity. Science, 2016, 353(6297), 399-403.
[http://dx.doi.org/10.1126/science.aae0477] [PMID: 27463676]
[106]
Kelderman, S.; Schumacher, T.N.; Haanen, J.B. Acquired and intrinsic resistance in cancer immunotherapy. Mol. Oncol., 2014, 8(6), 1132-1139.
[http://dx.doi.org/10.1016/j.molonc.2014.07.011] [PMID: 25106088]
[107]
Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; Ferrucci, P.F.; Hill, A.; Wagstaff, J.; Carlino, M.S.; Haanen, J.B.; Maio, M.; Marquez-Rodas, I.; McArthur, G.A.; Ascierto, P.A.; Long, G.V.; Callahan, M.K.; Postow, M.A.; Grossmann, K.; Sznol, M.; Dreno, B.; Bastholt, L.; Yang, A.; Rollin, L.M.; Horak, C.; Hodi, F.S.; Wolchok, J.D. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med., 2015, 373(1), 23-34.
[http://dx.doi.org/10.1056/NEJMoa1504030] [PMID: 26027431]
[108]
Robert, C.; Long, G.V.; Brady, B.; Dutriaux, C.; Maio, M.; Mortier, L.; Hassel, J.C.; Rutkowski, P.; McNeil, C.; Kalinka-Warzocha, E.; Savage, K.J.; Hernberg, M.M.; Lebbé, C.; Charles, J.; Mihalcioiu, C.; Chiarion-Sileni, V.; Mauch, C.; Cognetti, F.; Arance, A.; Schmidt, H.; Schadendorf, D.; Gogas, H.; Lundgren-Eriksson, L.; Horak, C.; Sharkey, B.; Waxman, I.M.; Atkinson, V.; Ascierto, P.A. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med., 2015, 372(4), 320-330.
[http://dx.doi.org/10.1056/NEJMoa1412082] [PMID: 25399552]
[109]
Restifo, N.P.; Smyth, M.J.; Snyder, A. Acquired resistance to immunotherapy and future challenges. Nat. Rev. Cancer, 2016, 16(2), 121-126.
[http://dx.doi.org/10.1038/nrc.2016.2] [PMID: 26822578]
[110]
Dai, B.; Xiao, L.; Bryson, P.D.; Fang, J.; Wang, P. PD-1/PD-L1 blockade can enhance HIV-1 Gag-specific T cell immunity elicited by dendritic cell-directed lentiviral vaccines. Mol. Ther., 2012, 20(9), 1800-1809.
[http://dx.doi.org/10.1038/mt.2012.98] [PMID: 22588271]
[111]
Day, C.L.; Kaufmann, D.E.; Kiepiela, P.; Brown, J.A.; Moodley, E.S.; Reddy, S.; Mackey, E.W.; Miller, J.D.; Leslie, A.J.; DePierres, C.; Mncube, Z.; Duraiswamy, J.; Zhu, B.; Eichbaum, Q.; Altfeld, M.; Wherry, E.J.; Coovadia, H.M.; Goulder, P.J.; Klenerman, P.; Ahmed, R.; Freeman, G.J.; Walker, B.D. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature, 2006, 443(7109), 350-354.
[http://dx.doi.org/10.1038/nature05115] [PMID: 16921384]
[112]
Van Allen, E.M.; Miao, D.; Schilling, B.; Shukla, S.A.; Blank, C.; Zimmer, L.; Sucker, A.; Hillen, U.; Foppen, M.H.G.; Goldinger, S.M.; Utikal, J.; Hassel, J.C.; Weide, B.; Kaehler, K.C.; Loquai, C.; Mohr, P.; Gutzmer, R.; Dummer, R.; Gabriel, S.; Wu, C.J.; Schadendorf, D.; Garraway, L.A. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science, 2015, 350(6257), 207-211.
[http://dx.doi.org/10.1126/science.aad0095] [PMID: 26359337]
[113]
Le, D.T.; Uram, J.N.; Wang, H.; Bartlett, B.R.; Kemberling, H.; Eyring, A.D.; Skora, A.D.; Luber, B.S.; Azad, N.S.; Laheru, D.; Biedrzycki, B.; Donehower, R.C.; Zaheer, A.; Fisher, G.A.; Crocenzi, T.S.; Lee, J.J.; Duffy, S.M.; Goldberg, R.M.; de la Chapelle, A.; Koshiji, M.; Bhaijee, F.; Huebner, T.; Hruban, R.H.; Wood, L.D.; Cuka, N.; Pardoll, D.M.; Papadopoulos, N.; Kinzler, K.W.; Zhou, S.; Cornish, T.C.; Taube, J.M.; Anders, R.A.; Eshleman, J.R.; Vogelstein, B.; Diaz, L.A., Jr PD-1 Blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med., 2015, 372(26), 2509-2520.
[http://dx.doi.org/10.1056/NEJMoa1500596] [PMID: 26028255]
[114]
Restifo, N.P.; Marincola, F.M.; Kawakami, Y.; Taubenberger, J.; Yannelli, J.R.; Rosenberg, S.A. Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J. Natl. Cancer Inst., 1996, 88(2), 100-108.
[http://dx.doi.org/10.1093/jnci/88.2.100] [PMID: 8537970]
[115]
Koyama, S.; Akbay, E.A.; Li, Y.Y.; Herter-Sprie, G.S.; Buczkowski, K.A.; Richards, W.G.; Gandhi, L.; Redig, A.J.; Rodig, S.J.; Asahina, H.; Jones, R.E.; Kulkarni, M.M.; Kuraguchi, M.; Palakurthi, S.; Fecci, P.E.; Johnson, B.E.; Janne, P.A.; Engelman, J.A.; Gangadharan, S.P.; Costa, D.B.; Freeman, G.J.; Bueno, R.; Hodi, F.S.; Dranoff, G.; Wong, K.K.; Hammerman, P.S. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat. Commun., 2016, 7, 10501.
[http://dx.doi.org/10.1038/ncomms10501] [PMID: 26883990]
[116]
Romero, D. Immunotherapy: PD-1 says goodbye, TIM-3 says hello. Nat. Rev. Clin. Oncol., 2016, 13(4), 202-203.
[http://dx.doi.org/10.1038/nrclinonc.2016.40] [PMID: 26977783]
[117]
Parsa, A.T.; Waldron, J.S.; Panner, A.; Crane, C.A.; Parney, I.F.; Barry, J.J.; Cachola, K.E.; Murray, J.C.; Tihan, T.; Jensen, M.C.; Mischel, P.S.; Stokoe, D.; Pieper, R.O. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat. Med., 2007, 13(1), 84-88.
[http://dx.doi.org/10.1038/nm1517] [PMID: 17159987]
[118]
Peng, W.; Chen, J.Q.; Liu, C.; Malu, S.; Creasy, C.; Tetzlaff, M.T.; Xu, C.; McKenzie, J.A.; Zhang, C.; Liang, X.; Williams, L.J.; Deng, W.; Chen, G.; Mbofung, R.; Lazar, A.J.; Torres-Cabala, C.A.; Cooper, Z.A.; Chen, P.L.; Tieu, T.N.; Spranger, S.; Yu, X.; Bernatchez, C.; Forget, M.A.; Haymaker, C.; Amaria, R.; McQuade, J.L.; Glitza, I.C.; Cascone, T.; Li, H.S.; Kwong, L.N.; Heffernan, T.P.; Hu, J.; Bassett, R.L., Jr; Bosenberg, M.W.; Woodman, S.E.; Overwijk, W.W.; Lizée, G.; Roszik, J.; Gajewski, T.F.; Wargo, J.A.; Gershenwald, J.E.; Radvanyi, L.; Davies, M.A.; Hwu, P. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov., 2016, 6(2), 202-216.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0283] [PMID: 26645196]
[119]
Peng, D.; Kryczek, I.; Nagarsheth, N.; Zhao, L.; Wei, S.; Wang, W.; Sun, Y.; Zhao, E.; Vatan, L.; Szeliga, W.; Kotarski, J.; Tarkowski, R.; Dou, Y.; Cho, K.; Hensley-Alford, S.; Munkarah, A.; Liu, R.; Zou, W. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature, 2015, 527(7577), 249-253.
[http://dx.doi.org/10.1038/nature15520] [PMID: 26503055]
[120]
Nagarsheth, N.; Peng, D.; Kryczek, I.; Wu, K.; Li, W.; Zhao, E.; Zhao, L.; Wei, S.; Frankel, T.; Vatan, L.; Szeliga, W.; Dou, Y.; Owens, S.; Marquez, V.; Tao, K.; Huang, E.; Wang, G.; Zou, W. PRC2 epigenetically silences Th1-type chemokines to suppress effector T-cell trafficking in colon cancer. Cancer Res., 2016, 76(2), 275-282.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1938] [PMID: 26567139]
[121]
Kugelberg, E. Tumour immunology: Reducing silence to improve therapy. Nat. Rev. Immunol., 2015, 15(12), 730.
[http://dx.doi.org/10.1038/nri3941] [PMID: 26542634]
[122]
Zajac, A.J.; Blattman, J.N.; Murali-Krishna, K.; Sourdive, D.J.; Suresh, M.; Altman, J.D.; Ahmed, R. Viral immune evasion due to persistence of activated T cells without effector function. J. Exp. Med., 1998, 188(12), 2205-2213.
[http://dx.doi.org/10.1084/jem.188.12.2205] [PMID: 9858507]
[123]
Wherry, E.J. T cell exhaustion. Nat. Immunol., 2011, 12(6), 492-499.
[http://dx.doi.org/10.1038/ni.2035] [PMID: 21739672]
[124]
Blackburn, S.D.; Shin, H.; Freeman, G.J.; Wherry, E.J. Selective expansion of a subset of exhausted CD8 T cells by alphaPD-L1 blockade. Proc. Natl. Acad. Sci. USA, 2008, 105(39), 15016-15021.
[http://dx.doi.org/10.1073/pnas.0801497105] [PMID: 18809920]
[125]
Barber, D.L.; Wherry, E.J.; Masopust, D.; Zhu, B.; Allison, J.P.; Sharpe, A.H.; Freeman, G.J.; Ahmed, R. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature, 2006, 439(7077), 682-687.
[http://dx.doi.org/10.1038/nature04444] [PMID: 16382236]
[126]
Patsoukis, N.; Bardhan, K.; Chatterjee, P.; Sari, D.; Liu, B.; Bell, L.N.; Karoly, E.D.; Freeman, G.J.; Petkova, V.; Seth, P.; Li, L.; Boussiotis, V.A. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat. Commun., 2015, 6, 6692.
[http://dx.doi.org/10.1038/ncomms7692] [PMID: 25809635]
[127]
Jiang, Y.; Li, Y.; Zhu, B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis., 2015, 6, e1792.
[http://dx.doi.org/10.1038/cddis.2015.162] [PMID: 26086965]
[128]
Curiel, T.J.; Wei, S.; Dong, H.; Alvarez, X.; Cheng, P.; Mottram, P.; Krzysiek, R.; Knutson, K.L.; Daniel, B.; Zimmermann, M.C.; David, O.; Burow, M.; Gordon, A.; Dhurandhar, N.; Myers, L.; Berggren, R.; Hemminki, A.; Alvarez, R.D.; Emilie, D.; Curiel, D.T.; Chen, L.; Zou, W. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat. Med., 2003, 9(5), 562-567.
[http://dx.doi.org/10.1038/nm863] [PMID: 12704383]
[129]
Kryczek, I.; Zou, L.; Rodriguez, P.; Zhu, G.; Wei, S.; Mottram, P.; Brumlik, M.; Cheng, P.; Curiel, T.; Myers, L.; Lackner, A.; Alvarez, X.; Ochoa, A.; Chen, L.; Zou, W. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J. Exp. Med., 2006, 203(4), 871-881.
[http://dx.doi.org/10.1084/jem.20050930] [PMID: 16606666]
[130]
Kim, K.; Skora, A.D.; Li, Z.; Liu, Q.; Tam, A.J.; Blosser, R.L.; Diaz, L.A., Jr Papadopoulos, N.; Kinzler, K.W.; Vogelstein, B.; Zhou, S. Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells. Proc. Natl. Acad. Sci. USA, 2014, 111(32), 11774-11779.
[http://dx.doi.org/10.1073/pnas.1410626111] [PMID: 25071169]
[131]
De Henau, O.; Rausch, M.; Winkler, D.; Campesato, L.F.; Liu, C.; Cymerman, D.H.; Budhu, S.; Ghosh, A.; Pink, M.; Tchaicha, J.; Douglas, M.; Tibbitts, T.; Sharma, S.; Proctor, J.; Kosmider, N.; White, K.; Stern, H.; Soglia, J.; Adams, J.; Palombella, V.J.; McGovern, K.; Kutok, J.L.; Wolchok, J.D.; Merghoub, T. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature, 2016, 539(7629), 443-447.
[http://dx.doi.org/10.1038/nature20554] [PMID: 27828943]
[132]
Schmid, M.C.; Avraamides, C.J.; Dippold, H.C.; Franco, I.; Foubert, P.; Ellies, L.G.; Acevedo, L.M.; Manglicmot, J.R.; Song, X.; Wrasidlo, W.; Blair, S.L.; Ginsberg, M.H.; Cheresh, D.A.; Hirsch, E.; Field, S.J.; Varner, J.A. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent point promoting tumor inflammation and progression. Cancer Cell, 2011, 19(6), 715-727.
[http://dx.doi.org/10.1016/j.ccr.2011.04.016] [PMID: 21665146]
[133]
Di Mitri, D.; Toso, A.; Alimonti, A. Molecular pathways: targeting tumor-infiltrating myeloid-derived suppressor cells for cancer therapy. Clin. Cancer Res., 2015, 21(14), 3108-3112.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2261] [PMID: 25967145]
[134]
Platten, M.; Wick, W.; Van den Eynde, B.J. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res., 2012, 72(21), 5435-5440.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-0569] [PMID: 23090118]
[135]
Prendergast, G.C.; Smith, C.; Thomas, S.; Mandik-Nayak, L.; Laury-Kleintop, L.; Metz, R.; Muller, A.J. Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer. Cancer Immunol. Immunother., 2014, 63(7), 721-735.
[http://dx.doi.org/10.1007/s00262-014-1549-4] [PMID: 24711084]
[136]
Holmgaard, R.B.; Zamarin, D.; Munn, D.H.; Wolchok, J.D.; Allison, J.P. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J. Exp. Med., 2013, 210(7), 1389-1402.
[http://dx.doi.org/10.1084/jem.20130066] [PMID: 23752227]
[137]
NCT02327078. ClinicalTrials.gov, 2016. [Updated 2016 July];
[138]
NCT01604889. ClinicalTrials.gov, 2016. [Updated 2016 July];
[139]
Viaud, S.; Saccheri, F.; Mignot, G.; Yamazaki, T.; Daillère, R.; Hannani, D.; Enot, D.P.; Pfirschke, C.; Engblom, C.; Pittet, M.J.; Schlitzer, A.; Ginhoux, F.; Apetoh, L.; Chachaty, E.; Woerther, P.L.; Eberl, G.; Bérard, M.; Ecobichon, C.; Clermont, D.; Bizet, C.; Gaboriau-Routhiau, V.; Cerf-Bensussan, N.; Opolon, P.; Yessaad, N.; Vivier, E.; Ryffel, B.; Elson, C.O.; Doré, J.; Kroemer, G.; Lepage, P.; Boneca, I.G.; Ghiringhelli, F.; Zitvogel, L. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science, 2013, 342(6161), 971-976.
[http://dx.doi.org/10.1126/science.1240537] [PMID: 24264990]
[140]
Iida, N.; Dzutsev, A.; Stewart, C.A.; Smith, L.; Bouladoux, N.; Weingarten, R.A.; Molina, D.A.; Salcedo, R.; Back, T.; Cramer, S.; Dai, R.M.; Kiu, H.; Cardone, M.; Naik, S.; Patri, A.K.; Wang, E.; Marincola, F.M.; Frank, K.M.; Belkaid, Y.; Trinchieri, G.; Goldszmid, R.S. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science, 2013, 342(6161), 967-970.
[http://dx.doi.org/10.1126/science.1240527] [PMID: 24264989]
[141]
Cho, I.; Blaser, M.J. The human microbiome: at the interface of health and disease. Nat. Rev. Genet., 2012, 13(4), 260-270.
[http://dx.doi.org/10.1038/nrg3182] [PMID: 22411464]
[142]
Spranger, S.; Bao, R.; Gajewski, T.F. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature, 2015, 523(7559), 231-235.
[http://dx.doi.org/10.1038/nature14404] [PMID: 25970248]
[143]
Klaus, A.; Birchmeier, W. Wnt signalling and its impact on development and cancer. Nat. Rev. Cancer, 2008, 8(5), 387-398.
[http://dx.doi.org/10.1038/nrc2389] [PMID: 18432252]
[144]
Ying, Y.; Tao, Q. Epigenetic disruption of the WNT/beta-catenin signaling pathway in human cancers. Epigenetics, 2009, 4(5), 307-312.
[http://dx.doi.org/10.4161/epi.4.5.9371] [PMID: 19633433]
[145]
Benhaj, K.; Akcali, K.C.; Ozturk, M. Redundant expression of canonical Wnt ligands in human breast cancer cell lines. Oncol. Rep., 2006, 15(3), 701-707.
[PMID: 16465433]
[146]
Nusse, R. Wnt signaling in disease and in development. Cell Res., 2005, 15(1), 28-32.
[http://dx.doi.org/10.1038/sj.cr.7290260] [PMID: 15686623]
[147]
Lugli, A.; Zlobec, I.; Minoo, P.; Baker, K.; Tornillo, L.; Terracciano, L.; Jass, J.R. Prognostic significance of the wnt signalling pathway molecules APC, beta-catenin and E-cadherin in colorectal cancer: a tissue microarray-based analysis. Histopathology, 2007, 50(4), 453-464.
[http://dx.doi.org/10.1111/j.1365-2559.2007.02620.x] [PMID: 17448021]
[148]
MacDonald, B.T.; Tamai, K.; He, X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev. Cell, 2009, 17(1), 9-26.
[http://dx.doi.org/10.1016/j.devcel.2009.06.016] [PMID: 19619488]
[149]
Wallingford, J.B.; Habas, R. The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity. Development, 2005, 132(20), 4421-4436.
[http://dx.doi.org/10.1242/dev.02068] [PMID: 16192308]
[150]
Schwarz-Romond, T.; Asbrand, C.; Bakkers, J.; Kühl, M.; Schaeffer, H.J.; Huelsken, J.; Behrens, J.; Hammerschmidt, M.; Birchmeier, W. The ankyrin repeat protein DIVERSIN recruits casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling. Genes Dev., 2002, 16(16), 2073-2084.
[http://dx.doi.org/10.1101/gad.230402] [PMID: 12183362]
[151]
He, T.C.; Sparks, A.B.; Rago, C.; Hermeking, H.; Zawel, L.; da Costa, L.T.; Morin, P.J.; Vogelstein, B.; Kinzler, K.W. Identification of c-MYC as a target of the APC pathway. Science, 1998, 281(5382), 1509-1512.
[http://dx.doi.org/10.1126/science.281.5382.1509] [PMID: 9727977]
[152]
Tetsu, O.; McCormick, F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature, 1999, 398(6726), 422-426.
[http://dx.doi.org/10.1038/18884] [PMID: 10201372]
[153]
Balkwill, F. Cancer and the chemokine network. Nat. Rev. Cancer, 2004, 4(7), 540-550.
[http://dx.doi.org/10.1038/nrc1388] [PMID: 15229479]
[154]
Khuu, C.H.; Barrozo, R.M.; Hai, T.; Weinstein, S.L. Activating transcription factor 3 (ATF3) represses the expression of CCL4 in murine macrophages. Mol. Immunol., 2007, 44(7), 1598-1605.
[http://dx.doi.org/10.1016/j.molimm.2006.08.006] [PMID: 16982098]
[155]
Yan, L.; Della Coletta, L.; Powell, K.L.; Shen, J.; Thames, H.; Aldaz, C.M.; MacLeod, M.C. Activation of the canonical Wnt/β-catenin pathway in ATF3-induced mammary tumors. PLoS One, 2011, 6(1), e16515.
[http://dx.doi.org/10.1371/journal.pone.0016515] [PMID: 21304988]
[156]
Hu-Lieskovan, S.; Homet Moreno, B.; Ribas, A.; Excluding, T.; Excluding, T. Cells: Is β-catenin the full story? Cancer Cell, 2015, 27(6), 749-750.
[http://dx.doi.org/10.1016/j.ccell.2015.05.014] [PMID: 26058073]
[157]
Kahn, M. Can we safely target the WNT pathway? Nat. Rev. Drug Discov., 2014, 13(7), 513-532.
[http://dx.doi.org/10.1038/nrd4233] [PMID: 24981364]
[158]
Jimmy Carter announces he is cancer-free. CNN, AVAILABLE AT: http://www.cnn.com/2015/12/06/politics/jimmy-carter-cancer-free/2016. [Updated 2016 July].
[159]
Survival statistics for malignant melanoma. Cancer Research UK, Available AT. http://www.cancerresearchuk. org/about-cancer/type/melanoma/treatment/melanoma-statistics-and-outlook2016. [Updated 2016 July].

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