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Review Article

Immunosuppression and Immunotargeted Therapy in Acute Myeloid Leukemia - The Potential Use of Checkpoint Inhibitors in Combination with Other Treatments

Author(s): Eva Leufven and Øystein Bruserud*

Volume 26, Issue 28, 2019

Page: [5244 - 5261] Pages: 18

DOI: 10.2174/0929867326666190325095853

Price: $65

Abstract

Introduction: Immunotherapy by using checkpoint inhibitors is now tried in the treatment of several malignancies, including Acute Myeloid Leukemia (AML). The treatment is tried both as monotherapy and as a part of combined therapy.

Methods: Relevant publications were identified through literature searches in the PubMed database. We searched for (i) original articles describing the results from clinical studies of checkpoint inhibition; (ii) published articles describing the immunocompromised status of AML patients; and (iii) published studies of antileukemic immune reactivity and immunotherapy in AML.

Results: Studies of monotherapy suggest that checkpoint inhibition has a modest antileukemic effect and complete hematological remissions are uncommon, whereas combination with conventional chemotherapy increases the antileukemic efficiency with acceptable toxicity. The experience with a combination of different checkpoint inhibitors is limited. Thalidomide derivatives are referred to as immunomodulatory drugs and seem to reverse leukemia-induced immunosuppression, but in addition, they have direct inhibitory effects on the AML cells. The combination of checkpoint targeting and thalidomide derivatives thus represents a strategy for dual immunotargeting together with a direct antileukemic effect.

Conclusion: Checkpoint inhibitors are now tried in AML. Experimental studies suggest that these inhibitors should be combined with immunomodulatory agents (i.e. thalidomide derivatives) and/or new targeted or conventional antileukemic treatment. Such combinations would allow dual immunotargeting (checkpoint inhibitor, immunomodulatory agents) together with a double/triple direct targeting of the leukemic cells.

Keywords: Acute myeloid leukemia, checkpoint inhibition, chemotherapy, immunotherapy, lenalidomide, targeted therapy.

« Previous Next »
[1]
Melve, G.K.; Ersvssr, E.; Kittang, A.O.; Bruserud, O. The chemokine system in allogeneic stem-cell transplantation: a possible therapeutic target? Expert Rev. Hematol., 2011, 4(5), 563-576.
[http://dx.doi.org/10.1586/ehm.11.54] [PMID: 21939423]
[2]
Blum, S.; Martins, F.; Lübbert, M. Immunotherapy in adult acute leukemia. Leuk. Res., 2017, 60, 63-73.
[http://dx.doi.org/10.1016/j.leukres.2017.06.011] [PMID: 28756350]
[3]
Knaus, H.A.; Kanakry, C.G.; Luznik, L.; Gojo, I. Immunomodulatory drugs: Immune checkpoint agents in acute leukemia. Curr. Drug Targets, 2017, 18(3), 315-331.
[http://dx.doi.org/10.2174/1389450116666150518095346] [PMID: 25981611]
[4]
Masarova, L.; Kantarjian, H.; Garcia-Mannero, G.; Ravandi, F.; Sharma, P.; Daver, N. Harnessing the immune system against leukemia: Monoclonal antibodies and checkpoint strategies for AML. Adv. Exp. Med. Biol., 2017, 995, 73-95.
[http://dx.doi.org/10.1007/978-3-319-53156-4_4] [PMID: 28321813]
[5]
Pardoll, D. Does the immune system see tumors as foreign or self? Annu. Rev. Immunol., 2003, 21, 807-839.
[http://dx.doi.org/10.1146/annurev.immunol.21.120601.141135] [PMID: 12615893]
[6]
Yee, C.; Thompson, J.A.; Byrd, D.; Riddell, S.R.; Roche, P.; Celis, E.; Greenberg, P.D. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc. Natl. Acad. Sci. USA, 2002, 99(25), 16168-16173.
[http://dx.doi.org/10.1073/pnas.242600099] [PMID: 12427970]
[7]
Moretti, S.; Pinzi, C.; Berti, E.; Spallanzani, A.; Chiarugi, A.; Boddi, V.; Reali, U.M.; Giannotti, B. In situ expression of transforming growth factor beta is associated with melanoma progression and correlates with Ki67, HLA-DR and beta 3 integrin expression. Melanoma Res., 1997, 7(4), 313-321.
[http://dx.doi.org/10.1097/00008390-199708000-00006] [PMID: 9293481]
[8]
Bogen, B. Peripheral T cell tolerance as a tumor escape mechanism: deletion of CD4+ T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma. Eur. J. Immunol., 1996, 26(11), 2671-2679.
[http://dx.doi.org/10.1002/eji.1830261119] [PMID: 8921954]
[9]
Lollini, P.L.; Nicoletti, G.; Landuzzi, L.; Cavallo, F.; Forni, G.; De Giovanni, C.; Nanni, P. Vaccines and other immunological approaches for cancer immunoprevention. Curr. Drug Targets, 2011, 12(13), 1957-1973.
[http://dx.doi.org/10.2174/138945011798184146] [PMID: 21158706]
[10]
Chu, N.J.; Armstrong, T.D.; Jaffee, E.M. Nonviral oncogenic antigens and the inflammatory signals driving early cancer development as targets for cancer immunoprevention. Clin. Cancer Res., 2015, 21(7), 1549-1557.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1186]
[11]
Wherry, E.J. T cell exhaustion. Nat. Immunol., 2011, 12(6), 492-499.
[http://dx.doi.org/10.1038/ni.2035] [PMID: 21739672]
[12]
Schnorfeil, F.M.; Lichtenegger, F.S.; Emmerig, K.; Schlueter, M.; Neitz, J.S.; Draenert, R.; Hiddemann, W.; Subklewe, M. T cells are functionally not impaired in AML: Increased PD-1 expression is only seen at time of relapse and correlates with a shift towards the memory T cell compartment. J. Hematol. Oncol., 2015, 8, 93.
[http://dx.doi.org/10.1186/s13045-015-0189-2] [PMID: 26219463]
[13]
Tan, J.; Chen, S.; Lu, Y.; Yao, D.; Xu, L.; Zhang, Y.; Yang, L.; Chen, J.; Lai, J.; Yu, Z.; Zhu, K.; Li, Y. Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients with de novo acute myeloid leukemia. Chin. J. Cancer Res., 2017, 29(5), 463-470.
[http://dx.doi.org/10.21147/j.issn.1000-9604.2017.05.11] [PMID: 29142466]
[14]
Olsnes, A.M.; Ersvaer, E.; Ryningen, A.; Bruserud, O. Circulating T cells derived from acute leukemia patients with severe therapy-induced cytopenia express a wide range of chemokine receptors. Hematology, 2008, 13(6), 329-332.
[http://dx.doi.org/10.1179/102453308X343491] [PMID: 19055860]
[15]
Ersvaer, E.; Liseth, K.; Skavland, J.; Gjertsen, B.T.; Bruserud, Ø. Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, TH1, TH17 and TREG cells. BMC Immunol., 2010, 11, 38.
[http://dx.doi.org/10.1186/1471-2172-11-38] [PMID: 20618967]
[16]
Wang, M.; Bu, J.; Zhou, M.; Sido, J.; Lin, Y.; Liu, G.; Lin, Q.; Xu, X.; Leavenworth, J.W.; Shen, E. CD8+T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients. Clin. Immunol., 2018, 190, 64-73.
[PMID: 28893624]
[17]
Yu, X.; Harden, K.; Gonzalez, L.C.; Francesco, M.; Chiang, E.; Irving, B.; Tom, I.; Ivelja, S.; Refino, C.J.; Clark, H.; Eaton, D.; Grogan, J.L. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat. Immunol., 2009, 10(1), 48-57.
[http://dx.doi.org/10.1038/ni.1674] [PMID: 19011627]
[18]
Bruserud, O.; Ulvestad, E.; Halstensen, A.; Berentsen, S.; Bergheim, J.; Nesthus, I. Interleukin 4 responses in acute leukaemia patients with severe chemotherapy-induced leucopenia. Eur. J. Haematol., 1997, 59(5), 269-276.
[http://dx.doi.org/10.1111/j.1600-0609.1997.tb01686.x] [PMID: 9414637]
[19]
Bruserud, O.; Pawelec, G. Interleukin-13 secretion by normal and posttransplant T lymphocytes; in vitro studies of cellular immune responses in the presence of acute leukaemia blast cells. Cancer Immunol. Immunother., 1997, 45(1), 45-52.
[http://dx.doi.org/10.1007/s002620050399] [PMID: 9353426]
[20]
Bruserud, O.; von Volkman, H.L.; Ulvestad, E. The cellular immune system of patients with acute leukemia and severe chemotherapy-induced leukopenia: characterization of T lymphocyte subsets responsive to IL-16 and IL-17. Acta Haematol., 2000, 104(2-3), 80-91.
[http://dx.doi.org/10.1159/000039756] [PMID: 11154979]
[21]
Bruserud, O.; Ulvestad, E. Cytokine responsiveness of mitogen-activated T cells derived from acute leukemia patients with chemotherapy-induced leukopenia. J. Interferon Cytokine Res., 2000, 20(11), 947-954.
[http://dx.doi.org/10.1089/10799900050198381] [PMID: 11096451]
[22]
Bruserud, O.; Ulvestad, E.; Berentsen, S.; Bergheim, J.; Nesthus, I. T-lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced cytopenia: characterization of clonogenic T-cell proliferation. Scand. J. Immunol., 1998, 47(1), 54-62.
[http://dx.doi.org/10.1046/j.1365-3083.1998.00254.x] [PMID: 9467659]
[23]
Bruserud, O.; Ulvestad, E. Acute myelogenous leukemia blasts as accessory cells during in vitro T lymphocyte activation. Cell. Immunol., 2000, 206(1), 36-50.
[http://dx.doi.org/10.1006/cimm.2000.1725] [PMID: 11161436]
[24]
Mackall, C.L. T-cell immunodeficiency following cytotoxic antineoplastic therapy: A review. Stem Cells, 2000, 18(1), 10-18.
[http://dx.doi.org/10.1634/stemcells.18-1-10] [PMID: 10661568]
[25]
Goswami, M.; Prince, G.; Biancotto, A.; Moir, S.; Kardava, L.; Santich, B.H.; Cheung, F.; Kotliarov, Y.; Chen, J.; Shi, R.; Zhou, H.; Golding, H.; Manischewitz, J.; King, L.; Kunz, L.M.; Noonan, K.; Borrello, I.M.; Smith, B.D.; Hourigan, C.S. Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy. J. Transl. Med., 2017, 15(1), 155.
[http://dx.doi.org/10.1186/s12967-017-1252-2] [PMID: 28693586]
[26]
Fredly, H.; Ersvær, E.; Kittang, A.O.; Tsykunova, G.; Gjertsen, B.T.; Bruserud, O. The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia. Clin. Epigenetics, 2013, 5(1), 13.
[http://dx.doi.org/10.1186/1868-7083-5-13] [PMID: 23915396]
[27]
Thoma, M.D.; Huneke, T.J.; DeCook, L.J.; Johnson, N.D.; Wiegand, R.A.; Litzow, M.R.; Hogan, W.J.; Porrata, L.F.; Holtan, S.G. Peripheral blood lymphocyte and monocyte recovery and survival in acute leukemia postmyeloablative allogeneic hematopoietic stem cell transplant. Biol. Blood Marrow Transplant., 2012, 18(4), 600-607.
[http://dx.doi.org/10.1016/j.bbmt.2011.08.007] [PMID: 21843495]
[28]
Behl, D.; Porrata, L.F.; Markovic, S.N.; Letendre, L.; Pruthi, R.K.; Hook, C.C.; Tefferi, A.; Elliot, M.A.; Kaufmann, S.H.; Mesa, R.A.; Litzow, M.R. Absolute lymphocyte count recovery after induction chemotherapy predicts superior survival in acute myelogenous leukemia. Leukemia, 2006, 20(1), 29-34.
[http://dx.doi.org/10.1038/sj.leu.2404032] [PMID: 16281063]
[29]
Porrata, L.F.; Litzow, M.R.; Tefferi, A.; Letendre, L.; Kumar, S.; Geyer, S.M.; Markovic, S.N. Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia. Leukemia, 2002, 16(7), 1311-1318.
[http://dx.doi.org/10.1038/sj.leu.2402503] [PMID: 12094255]
[30]
Döhner, H.; Estey, E.; Grimwade, D.; Amadori, S.; Appelbaum, F.R.; Büchner, T.; Dombret, H.; Ebert, B.L.; Fenaux, P.; Larson, R.A.; Levine, R.L.; Lo-Coco, F.; Naoe, T.; Niederwieser, D.; Ossenkoppele, G.J.; Sanz, M.; Sierra, J.; Tallman, M.S.; Tien, H.F.; Wei, A.H.; Löwenberg, B.; Bloomfield, C.D. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood, 2017, 129(4), 424-447.
[http://dx.doi.org/10.1182/blood-2016-08-733196] [PMID: 27895058]
[31]
Cornelissen, J.J.; Gratwohl, A.; Schlenk, R.F.; Sierra, J.; Bornhäuser, M.; Juliusson, G.; Råcil, Z.; Rowe, J.M.; Russell, N.; Mohty, M.; Löwenberg, B.; Socié, G.; Niederwieser, D.; Ossenkoppele, G.J. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat. Rev. Clin. Oncol., 2012, 9(10), 579-590.
[http://dx.doi.org/10.1038/nrclinonc.2012.150] [PMID: 22949046]
[32]
Podoltsev, N.A.; Stahl, M.; Zeidan, A.M.; Gore, S.D. Selecting initial treatment of acute myeloid leukaemia in older adults. Blood Rev., 2017, 31(2), 43-62.
[http://dx.doi.org/10.1016/j.blre.2016.09.005] [PMID: 27745715]
[33]
Bose, P.; Vachhani, P.; Cortes, J.E. Treatment of relapsed/refractory acute myeloid leukemia. Curr. Treat. Options Oncol., 2017, 18(3), 17.
[http://dx.doi.org/10.1007/s11864-017-0456-2] [PMID: 28286924]
[34]
Fredly, H.; Gjertsen, B.T.; Bruserud, O. Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents. Clin. Epigenetics, 2013, 5(1), 12.
[http://dx.doi.org/10.1186/1868-7083-5-12] [PMID: 23898968]
[35]
Sheng, J.; Srivastava, S.; Sanghavi, K.; Lu, Z.; Schmidt, B.J.; Bello, A.; Gupta, M. Clinical pharmacology considerations for the development of immune checkpoint inhibitors. J. Clin. Pharmacol., 2017, 57(Suppl. 10), S26-S42.
[http://dx.doi.org/10.1002/jcph.990] [PMID: 28921644]
[36]
Myers, G. Immune-related adverse events of immune checkpoint inhibitors: A brief review. Curr. Oncol., 2018, 25(5), 342-347.
[http://dx.doi.org/10.3747/co.25.4235] [PMID: 30464684]
[37]
Kumar, V.; Chaudhary, N.; Garg, M.; Floudas, C.S.; Soni, P.; Chandra, A.B. Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy. Front. Pharmacol., 2017, 8, 49.
[http://dx.doi.org/10.3389/fphar.2017.00049] [PMID: 28228726]
[38]
El Majzoub, I.; Qdaisat, A.; Thein, K.Z.; Win, M.A.; Han, M.M.; Jacobson, K.; Chaftari, P.S.; Prejean, M.; Reyes-Gibby, C.; Yeung, S.J. Adverse effects of immune checkpoint therapy in cancer patients visiting the emergency department of a comprehensive cancer center. Ann. Emerg. Med., 2019, 73(1), 79-87.
[PMID: 29880440]
[39]
Ok, C.Y.; Young, K.H. Checkpoint inhibitors in hematological malignancies. J. Hematol. Oncol., 2017, 10(1), 103.
[http://dx.doi.org/10.1186/s13045-017-0474-3] [PMID: 28482851]
[40]
Boddu, P.; Kantarjian, H.; Garcia-Manero, G.; Allison, J.; Sharma, P.; Daver, N. The emerging role of immune checkpoint based approaches in AML and MDS. Leuk. Lymphoma, 2018, 59(4), 790-802.
[PMID: 28679300]
[41]
Rudd, C.E.; Taylor, A.; Schneider, H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol. Rev., 2009, 229(1), 12-26.
[http://dx.doi.org/10.1111/j.1600-065X.2009.00770.x] [PMID: 19426212]
[42]
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]
[43]
Ryan, J.M.; Wasser, J.S.; Adler, A.J.; Vella, A.T. Enhancing the safety of antibody-based immunomodulatory cancer therapy without compromising therapeutic benefit: Can we have our cake and eat it too? Expert Opin. Biol. Ther., 2016, 16(5), 655-674.
[http://dx.doi.org/10.1517/14712598.2016.1152256] [PMID: 26855028]
[44]
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]
[45]
Pérez-García, A.; Brunet, S.; Berlanga, J.J.; Tormo, M.; Nomdedeu, J.; Guardia, R.; Ribera, J.M.; Heras, I.; Llorente, A.; Hoyos, M.; Esteve, J.; Besalduch, J.; Bueno, J.; Sierra, J.; Gallardo, D. CTLA-4 genotype and relapse incidence in patients with acute myeloid leukemia in first complete remission after induction chemotherapy. Leukemia, 2009, 23(3), 486-491.
[http://dx.doi.org/10.1038/leu.2008.339] [PMID: 19092854]
[46]
Poh, S.L.; Linn, Y.C. Immune checkpoint inhibitors enhance cytotoxicity of cytokine-induced killer cells against human myeloid leukaemic blasts. Cancer Immunol. Immunother., 2016, 65(5), 525-536.
[http://dx.doi.org/10.1007/s00262-016-1815-8] [PMID: 26961084]
[47]
Sander, F.E.; Nilsson, M.; Rydström, A.; Aurelius, J.; Riise, R.E.; Movitz, C.; Bernson, E.; Kiffin, R.; Ståhlberg, A.; Brune, M.; Foà, R.; Hellstrand, K.; Thorén, F.B.; Martner, A. Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy. Cancer Immunol. Immunother., 2017, 66(11), 1473-1484.
[http://dx.doi.org/10.1007/s00262-017-2040-9] [PMID: 28721449]
[48]
Zhong, R.K.; Loken, M.; Lane, T.A.; Ball, E.D. CTLA-4 blockade by a human MAb enhances the capacity of AML-derived DC to induce T-cell responses against AML cells in an autologous culture system. Cytotherapy, 2006, 8(1), 3-12.
[http://dx.doi.org/10.1080/14653240500499507] [PMID: 16627340]
[49]
Olsnes, A.M.; Ryningen, A.; Ersvaer, E.; Bruserud, Ø. In vitro induction of a dendritic cell phenotype in primary human acute myelogenous leukemia (AML) blasts alters the chemokine release profile and increases the levels of T cell chemotactic CCL17 and CCL22. J. Interferon Cytokine Res., 2008, 28(5), 297-310.
[http://dx.doi.org/10.1089/jir.2007.0052] [PMID: 18547160]
[50]
Pistillo, M.P.; Tazzari, P.L.; Palmisano, G.L.; Pierri, I.; Bolognesi, A.; Ferlito, F.; Capanni, P.; Polito, L.; Ratta, M.; Pileri, S.; Piccioli, M.; Basso, G.; Rissotto, L.; Conte, R.; Gobbi, M.; Stirpe, F.; Ferrara, G.B. CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells. Blood, 2003, 101(1), 202-209.
[http://dx.doi.org/10.1182/blood-2002-06-1668] [PMID: 12393538]
[51]
Laurent, S.; Palmisano, G.L.; Martelli, A.M.; Kato, T.; Tazzari, P.L.; Pierri, I.; Clavio, M.; Dozin, B.; Balbi, G.; Megna, M.; Morabito, A.; Lamparelli, T.; Bacigalupo, A.; Gobbi, M.; Pistillo, M.P. CTLA-4 expressed by chemoresistant, as well as untreated, myeloid leukaemia cells can be targeted with ligands to induce apoptosis. Br. J. Haematol., 2007, 136(4), 597-608.
[http://dx.doi.org/10.1111/j.1365-2141.2006.06472.x] [PMID: 17367412]
[52]
Sengsayadeth, S.; Wang, T.; Lee, S.J.; Haagenson, M.D.; Spellman, S.; Fernandez Viña, M.A.; Muller, C.R.; Verneris, M.R.; Savani, B.N.; Jagasia, M. Cytotoxic T-lymphocyte antigen-4 single nucleotide polymorphisms are not associated with outcomes after unrelated donor transplantation: a center for international blood and marrow transplant research analysis. Biol. Blood Marrow Transplant., 2014, 20(6), 900-903.
[http://dx.doi.org/10.1016/j.bbmt.2014.03.005] [PMID: 24631737]
[53]
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]
[54]
Zhou, Q.; Munger, M.E.; Highfill, S.L.; Tolar, J.; Weigel, B.J.; Riddle, M.; Sharpe, A.H.; Vallera, D.A.; Azuma, M.; Levine, B.L.; June, C.H.; Murphy, W.J.; Munn, D.H.; Blazar, B.R. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood, 2010, 116(14), 2484-2493.
[http://dx.doi.org/10.1182/blood-2010-03-275446] [PMID: 20570856]
[55]
Zhang, L.; Gajewski, T.F.; Kline, J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood, 2009, 114(8), 1545-1552.
[http://dx.doi.org/10.1182/blood-2009-03-206672] [PMID: 19417208]
[56]
Zhou, Q.; Munger, M.E.; Veenstra, R.G.; Weigel, B.J.; Hirashima, M.; Munn, D.H.; Murphy, W.J.; Azuma, M.; Anderson, A.C.; Kuchroo, V.K.; Blazar, B.R. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood, 2011, 117(17), 4501-4510.
[http://dx.doi.org/10.1182/blood-2010-10-310425] [PMID: 21385853]
[57]
Schmohl, J.U.; Nuebling, T.; Wild, J.; Kroell, T.; Kanz, L.; Salih, H.R.; Schmetzer, H. Expression of RANK-L and in part of PD-1 on blasts in patients with acute myeloid leukemia correlates with prognosis. Eur. J. Haematol., 2016, 97(6), 517-527.
[http://dx.doi.org/10.1111/ejh.12762] [PMID: 27096305]
[58]
Pyzer, A.R.; Stroopinsky, D.; Rosenblatt, J.; Anastasiadou, E.; Rajabi, H.; Washington, A.; Tagde, A.; Chu, J.H.; Coll, M.; Jiao, A.L.; Tsai, L.T.; Tenen, D.E.; Cole, L.; Palmer, K.; Ephraim, A.; Leaf, R.K.; Nahas, M.; Apel, A.; Bar-Natan, M.; Jain, S.; McMasters, M.; Mendez, L.; Arnason, J.; Raby, B.A.; Slack, F.; Kufe, D.; Avigan, D. MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs. Leukemia, 2017, 31(12), 2780-2790.
[http://dx.doi.org/10.1038/leu.2017.163] [PMID: 28555079]
[59]
Goltz, D.; Gevensleben, H.; Dietrich, J.; Dietrich, D. PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients. OncoImmunology, 2016, 6(1)e1257454
[http://dx.doi.org/10.1080/2162402X.2016.1257454] [PMID: 28197377]
[60]
Ørskov, A.D.; Treppendahl, M.B.; Skovbo, A.; Holm, M.S.; Friis, L.S.; Hokland, M.; Grønbæk, K. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients: A rationale for combined targeting of PD-1 and DNA methylation. Oncotarget, 2015, 6(11), 9612-9626.
[http://dx.doi.org/10.18632/oncotarget.3324] [PMID: 25823822]
[61]
Yang, H.; Bueso-Ramos, C.; DiNardo, C.; Estecio, M.R.; Davanlou, M.; Geng, Q.R.; Fang, Z.; Nguyen, M.; Pierce, S.; Wei, Y.; Parmar, S.; Cortes, J.; Kantarjian, H.; Garcia-Manero, G. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia, 2014, 28(6), 1280-1288.
[http://dx.doi.org/10.1038/leu.2013.355] [PMID: 24270737]
[62]
Krupka, C.; Kufer, P.; Kischel, R.; Zugmaier, G.; Lichtenegger, F.S.; Köhnke, T.; Vick, B.; Jeremias, I.; Metzeler, K.H.; Altmann, T.; Schneider, S.; Fiegl, M.; Spiekermann, K.; Bauerle, P.A.; Hiddemann, W.; Riethmüller, G.; Subklewe, M. Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: Reversing a T-cell-induced immune escape mechanism. Leukemia, 2016, 30(2), 484-491.
[http://dx.doi.org/10.1038/leu.2015.214] [PMID: 26239198]
[63]
Kong, Y.; Zhang, J.; Claxton, D.F.; Ehmann, W.C.; Rybka, W.B.; Zhu, L.; Zeng, H.; Schell, T.D.; Zheng, H. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J., 2015, 5e330
[http://dx.doi.org/10.1038/bcj.2015.58] [PMID: 26230954]
[64]
Sundar, R.; Cho, B.C.; Brahmer, J.R.; Soo, R.A. Nivolumab in NSCLC: latest evidence and clinical potential. Ther. Adv. Med. Oncol., 2015, 7(2), 85-96.
[http://dx.doi.org/10.1177/1758834014567470] [PMID: 25755681]
[65]
Curran, M.A.; Montalvo, W.; Yagita, H.; Allison, J.P. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc. Natl. Acad. Sci. USA, 2010, 107(9), 4275-4280.
[http://dx.doi.org/10.1073/pnas.0915174107] [PMID: 20160101]
[66]
Krönig, H.; Kremmler, L.; Haller, B.; Englert, C.; Peschel, C.; Andreesen, R.; Blank, C.U. Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment. Eur. J. Haematol., 2014, 92(3), 195-203.
[http://dx.doi.org/10.1111/ejh.12228] [PMID: 24175978]
[67]
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]
[68]
Chen, X.; Liu, S.; Wang, L.; Zhang, W.; Ji, Y.; Ma, X. Clinical significance of B7-H1 (PD-L1) expression in human acute leukemia. Cancer Biol. Ther., 2008, 7(5), 622-627.
[http://dx.doi.org/10.4161/cbt.7.5.5689] [PMID: 18756622]
[69]
Mussai, F.; De Santo, C.; Abu-Dayyeh, I.; Booth, S.; Quek, L.; McEwen-Smith, R.M.; Qureshi, A.; Dazzi, F.; Vyas, P.; Cerundolo, V. Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood, 2013, 122(5), 749-758.
[http://dx.doi.org/10.1182/blood-2013-01-480129] [PMID: 23733335]
[70]
Samuchiwal, S.K.; Balestrieri, B.; Raff, H.; Boyce, J.A. Endogenous prostaglandin E2 amplifies IL-33 production by macrophages through an E prostanoid (EP)2/EP4-cAMP-EPAC-dependent pathway. J. Biol. Chem., 2017, 292(20), 8195-8206.
[http://dx.doi.org/10.1074/jbc.M116.769422] [PMID: 28341741]
[71]
Zeng, K.; Deng, B.P.; Jiang, H.Q.; Wang, M.; Hua, P.; Zhang, H.W.; Deng, Y.B.; Yang, Y.Q.; Prostaglandin, E. Prostaglandin E1 protects bone marrow-derived mesenchymal stem cells against serum deprivation-induced apoptosis. Mol. Med. Rep., 2015, 12(4), 5723-5729.
[http://dx.doi.org/10.3892/mmr.2015.4176] [PMID: 26252504]
[72]
Iachininoto, M.G.; Nuzzolo, E.R.; Bonanno, G.; Mariotti, A.; Procoli, A.; Locatelli, F.; De Cristofaro, R.; Rutella, S. Cyclooxygenase-2 (COX-2) inhibition constrains indoleamine 2,3-dioxygenase 1 (IDO1) activity in acute myeloid leukaemia cells. Molecules, 2013, 18(9), 10132-10145.
[http://dx.doi.org/10.3390/molecules180910132] [PMID: 23973990]
[73]
Naderi, E.H.; Skah, S.; Ugland, H.; Myklebost, O.; Sandnes, D.L.; Torgersen, M.L.; Josefsen, D.; Ruud, E.; Naderi, S.; Blomhoff, H.K. Bone marrow stroma-derived PGE2 protects BCP-ALL cells from DNA damage-induced p53 accumulation and cell death. Mol. Cancer, 2015, 14, 14.
[http://dx.doi.org/10.1186/s12943-014-0278-9] [PMID: 25623255]
[74]
Fallarino, F.; Grohmann, U.; You, S.; McGrath, B.C.; Cavener, D.R.; Vacca, C.; Orabona, C.; Bianchi, R.; Belladonna, M.L.; Volpi, C.; Santamaria, P.; Fioretti, M.C.; Puccetti, P. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J. Immunol., 2006, 176(11), 6752-6761.
[http://dx.doi.org/10.4049/jimmunol.176.11.6752] [PMID: 16709834]
[75]
Curti, A.; Pandolfi, S.; Valzasina, B.; Aluigi, M.; Isidori, A.; Ferri, E.; Salvestrini, V.; Bonanno, G.; Rutella, S.; Durelli, I.; Horenstein, A.L.; Fiore, F.; Massaia, M.; Colombo, M.P.; Baccarani, M.; Lemoli, R.M. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Blood, 2007, 109(7), 2871-2877.
[PMID: 17164341]
[76]
Mellor, A.L.; Lemos, H.; Huang, L. Indoleamine 2,3-dioxygenase and tolerance: Where are we now? Front. Immunol., 2017, 8, 1360.
[http://dx.doi.org/10.3389/fimmu.2017.01360] [PMID: 29163470]
[77]
Locafaro, G.; Amodio, G.; Tomasoni, D.; Tresoldi, C.; Ciceri, F.; Gregori, S. HLA-G expression on blasts and tolerogenic cells in patients affected by acute myeloid leukemia. J. Immunol. Res., 2014, 2014636292
[http://dx.doi.org/10.1155/2014/636292] [PMID: 24741612]
[78]
Szczepanski, M.J.; Szajnik, M.; Czystowska, M.; Mandapathil, M.; Strauss, L.; Welsh, A.; Foon, K.A.; Whiteside, T.L.; Boyiadzis, M. Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin. Cancer Res., 2009, 15(10), 3325-3332.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-3010]
[79]
Ustun, C.; Miller, J.S.; Munn, D.H.; Weisdorf, D.J.; Blazar, B.R. Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation? Blood, 2011, 118(19), 5084-5095.
[http://dx.doi.org/10.1182/blood-2011-07-365817] [PMID: 21881045]
[80]
Whiteside, T.L. Induced regulatory T cells in inhibitory microenvironments created by cancer. Expert Opin. Biol. Ther., 2014, 14(10), 1411-1425.
[http://dx.doi.org/10.1517/14712598.2014.927432] [PMID: 24934899]
[81]
Brenner, A.K.; Tvedt, T.H.; Nepstad, I.; Rye, K.P.; Hagen, K.M.; Reikvam, H.; Bruserud, Ø. Patients with acute myeloid leukemia can be subclassified based on the constitutive cytokine release of the leukemic cells; the possible clinical relevance and the importance of cellular iron metabolism. Expert Opin. Ther. Targets, 2017, 21(4), 357-369.
[http://dx.doi.org/10.1080/14728222.2017.1300255] [PMID: 28281897]
[82]
Kittang, A.O.; Kordasti, S.; Sand, K.E.; Costantini, B.; Kramer, A.M.; Perezabellan, P.; Seidl, T.; Rye, K.P.; Hagen, K.M.; Kulasekararaj, A.; Bruserud, Ø.; Mufti, G.J. Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome. OncoImmunology, 2015, 5(2)e1062208
[http://dx.doi.org/10.1080/2162402X.2015.1062208] [PMID: 27057428]
[83]
Bruserud, Ø.; Ryningen, A.; Olsnes, A.M.; Stordrange, L.; Øyan, A.M.; Kalland, K.H.; Gjertsen, B.T. Subclassification of patients with acute myelogenous leukemia based on chemokine responsiveness and constitutive chemokine release by their leukemic cells. Haematologica, 2007, 92(3), 332-341.
[http://dx.doi.org/10.3324/haematol.10148] [PMID: 17339182]
[84]
Honnemyr, M.; Bruserud, Ø.; Brenner, A.K. The constitutive protease release by primary human acute myeloid leukemia cells. J. Cancer Res. Clin. Oncol., 2017, 143(10), 1985-1998.
[http://dx.doi.org/10.1007/s00432-017-2458-7] [PMID: 28631213]
[85]
Biswas, S.K.; Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol., 2010, 11(10), 889-896.
[http://dx.doi.org/10.1038/ni.1937] [PMID: 20856220]
[86]
Cheung, T.S.; Dazzi, F. Mesenchymal-myeloid interaction in the regulation of immunity. Semin. Immunol., 2018, 35, 59-68.
[http://dx.doi.org/10.1016/j.smim.2018.01.002] [PMID: 29395680]
[87]
Wang, Y.; Chen, X.; Cao, W.; Shi, Y. Plasticity of mesenchymal stem cells in immunomodulation: Pathological and therapeutic implications. Nat. Immunol., 2014, 15(11), 1009-1016.
[http://dx.doi.org/10.1038/ni.3002] [PMID: 25329189]
[88]
Al-Soudi, A.; Kaaij, M.H.; Tas, S.W. Endothelial cells: From innocent bystanders to active participants in immune responses. Autoimmun. Rev., 2017, 16(9), 951-962.
[http://dx.doi.org/10.1016/j.autrev.2017.07.008] [PMID: 28698091]
[89]
Navarro, R.; Compte, M.; Álvarez-Vallina, L.; Sanz, L. Immune regulation by pericytes: Modulating innate and adaptive immunity. Front. Immunol., 2016, 7, 480.
[http://dx.doi.org/10.3389/fimmu.2016.00480] [PMID: 27867386]
[90]
Brenner, A.K.; Andersson Tvedt, T.H.; Bruserud, Ø. The complexity of targeting PI3K-Akt-mTOR signalling in human acute myeloid leukaemia: The importance of leukemic cell heterogeneity, neighbouring mesenchymal stem cells and immunocompetent cells. Molecules, 2016, 21(11)E1512
[http://dx.doi.org/10.3390/molecules21111512] [PMID: 27845732]
[91]
Sehgal, A.; Whiteside, T.L.; Boyiadzis, M. Programmed death-1 checkpoint blockade in acute myeloid leukemia. Expert Opin. Biol. Ther., 2015, 15(8), 1191-1203.
[http://dx.doi.org/10.1517/14712598.2015.1051028] [PMID: 26036819]
[92]
Linn, Y.C.; Lau, L.C.; Hui, K.M. Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Br. J. Haematol., 2002, 116(1), 78-86.
[http://dx.doi.org/10.1046/j.1365-2141.2002.03247.x] [PMID: 11841399]
[93]
Khaznadar, Z.; Henry, G.; Setterblad, N.; Agaugue, S.; Raffoux, E.; Boissel, N.; Dombret, H.; Toubert, A.; Dulphy, N. Acute myeloid leukemia impairs natural killer cells through the formation of a deficient cytotoxic immunological synapse. Eur. J. Immunol., 2014, 44(10), 3068-3080.
[http://dx.doi.org/10.1002/eji.201444500] [PMID: 25041786]
[94]
Itchaki, G.; Brown, J.R. Lenalidomide in the treatment of chronic lymphocytic leukemia. Expert Opin. Investig. Drugs, 2017, 26(5), 633-650.
[http://dx.doi.org/10.1080/13543784.2017.1313230] [PMID: 28388253]
[95]
Richardson, P.G.; Holstein, S.A.; Schlossman, R.L.; Anderson, K.C.; Attal, M.; McCarthy, P.L. Lenalidomide in combination or alone as maintenance therapy following autologous stem cell transplant in patients with multiple myeloma: A review of options for and against. Expert Opin. Pharmacother., 2017, 18(18), 1975-1985.
[http://dx.doi.org/10.1080/14656566.2017.1409207] [PMID: 29172855]
[96]
Zeidner, J.F.; Foster, M.C. Immunomodulatory drugs: IMiDs in Acute Myeloid Leukemia (AML). Curr. Drug Targets, 2017, 18(3), 304-314.
[http://dx.doi.org/10.2174/1389450116666150304104315] [PMID: 25738295]
[97]
Chen, Y.; Borthakur, G. Lenalidomide as a novel treatment of acute myeloid leukemia. Expert Opin. Investig. Drugs, 2013, 22(3), 389-397.
[http://dx.doi.org/10.1517/13543784.2013.758712] [PMID: 23316859]
[98]
Ghosh, N.; Grunwald, M.R.; Fasan, O.; Bhutani, M. Expanding role of lenalidomide in hematologic malignancies. Cancer Manag. Res., 2015, 7, 105-119.
[http://dx.doi.org/10.2147/CMAR.S81310] [PMID: 25999761]
[99]
Blum, W.; Klisovic, R.B.; Becker, H.; Yang, X.; Rozewski, D.M.; Phelps, M.A.; Garzon, R.; Walker, A.; Chandler, J.C.; Whitman, S.P.; Curfman, J.; Liu, S.; Schaaf, L.; Mickle, J.; Kefauver, C.; Devine, S.M.; Grever, M.R.; Marcucci, G.; Byrd, J.C. Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J. Clin. Oncol., 2010, 28(33), 4919-4925.
[http://dx.doi.org/10.1200/JCO.2010.30.3339] [PMID: 20956622]
[100]
Fehniger, T.A.; Byrd, J.C.; Marcucci, G.; Abboud, C.N.; Kefauver, C.; Payton, J.E.; Vij, R.; Blum, W. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood, 2009, 113(5), 1002-1005.
[http://dx.doi.org/10.1182/blood-2008-04-152678] [PMID: 18824593]
[101]
Fehniger, T.A.; Uy, G.L.; Trinkaus, K.; Nelson, A.D.; Demland, J.; Abboud, C.N.; Cashen, A.F.; Stockerl-Goldstein, K.E.; Westervelt, P.; DiPersio, J.F.; Vij, R. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood, 2011, 117(6), 1828-1833.
[http://dx.doi.org/10.1182/blood-2010-07-297143] [PMID: 21051557]
[102]
Chen, Y.; Kantarjian, H.; Estrov, Z.; Faderl, S.; Ravandi, F.; Rey, K.; Cortes, J.; Borthakur, G. A phase II study of lenalidomide alone in relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndromes with chromosome 5 abnormalities. Clin. Lymphoma Myeloma Leuk., 2012, 12(5), 341-344.
[http://dx.doi.org/10.1016/j.clml.2012.04.001] [PMID: 22579233]
[103]
Medeiros, B.C.; McCaul, K.; Kambhampati, S.; Pollyea, D.A.; Kumar, R.; Silverman, L.R.; Kew, A.; Saini, L.; Beach, C.L.; Vij, R.; Wang, X.; Zhong, J.; Gale, R.P. Randomized study of continuous high-dose lenalidomide, sequential azacitidine and lenalidomide, or azacitidine in persons 65 years and over with newly-diagnosed acute myeloid leukemia. Haematologica, 2018, 103(1), 101-106.
[http://dx.doi.org/10.3324/haematol.2017.172353] [PMID: 29097499]
[104]
DiNardo, C.D.; Daver, N.; Jabbour, E.; Kadia, T.; Borthakur, G.; Konopleva, M.; Pemmaraju, N.; Yang, H.; Pierce, S.; Wierda, W.; Bueso-Ramos, C.; Patel, K.P.; Cortes, J.E.; Ravandi, F.; Kantarjian, H.M.; Garcia-Manero, G. Sequential azacitidine and lenalidomide in patients with high-risk myelodysplastic syndromes and acute myeloid leukaemia: a single-arm, phase 1/2 study. Lancet Haematol., 2015, 2(1), e12-e20.
[http://dx.doi.org/10.1016/S2352-3026(14)00026-X] [PMID: 26687423]
[105]
Visani, G.; Ferrara, F.; Di Raimondo, F.; Loscocco, F.; Fuligni, F.; Paolini, S.; Zammit, V.; Spina, E.; Rocchi, M.; Visani, A.; Piccaluga, P.P.; Isidori, A. Low-dose lenalidomide plus cytarabine in very elderly, unfit acute myeloid leukemia patients: Final result of a phase II study. Leuk. Res., 2017, 62, 77-83.
[http://dx.doi.org/10.1016/j.leukres.2017.09.019] [PMID: 28987821]
[106]
Griffiths, E.A.; Brady, W.E.; Tan, W.; Vigil, C.E.; Thompson, J.E.; Ford, L.A.; Dickey, N.M.; L, Bashaw. H.; Sperrazza, J.; Wetzler, M.; Wang, E.S. A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia. Leuk. Res., 2016, 43, 44-48.
[http://dx.doi.org/10.1016/j.leukres.2016.02.003] [PMID: 26943703]
[107]
Hunault-Berger, M.; Maillard, N.; Himberlin, C.; Recher, C.; Schmidt-Tanguy, A.; Choufi, B.; Bonmati, C.; Carré, M.; Couturier, M.A.; Daguindau, E.; Marolleau, J.P.; Orsini-Piocelle, F.; Delaunay, J.; Tavernier, E.; Lissandre, S.; Ojeda-Uribe, M.; Sanhes, L.; Sutton, L.; Banos, A.; Fornecker, L.M.; Bernard, M.; Bouscary, D.; Saad, A.; Puyade, M.; Rouillé, V.; Luquet, I.; Béné, M.C.; Hamel, J.F.; Dreyfus, F.; Ifrah, N.; Pigneux, A. Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial. Blood Cancer J., 2017, 7(6)e568
[http://dx.doi.org/10.1038/bcj.2017.50] [PMID: 28574488]
[108]
Ades, L.; Prebet, T.; Stamatoullas, A.; Recher, C.; Guieze, R.; Raffoux, E.; Bouabdallah, K.; Hunault, M.; Wattel, E.; Stalnikiewicz, L.; Toma, A.; Dombret, H.; Vey, N.; Sebert, M.; Gardin, C.; Chaffaut, C.; Chevret, S.; Fenaux, P. Lenalidomide combined with intensive chemotherapy in acute myeloid leukemia and higher-risk myelodysplastic syndrome with 5q deletion. Results of a phase II study by the Groupe Francophone Des Myélodysplasies. Haematologica, 2017, 102(4), 728-735.
[http://dx.doi.org/10.3324/haematol.2016.151894] [PMID: 28034993]
[109]
Riches, J.C.; Gribben, J.G. Mechanistic and clinical aspects of lenalidomide treatment for chronic lymphocytic leukemia. Curr. Cancer Drug Targets, 2016, 16(8), 689-700.
[http://dx.doi.org/10.2174/1568009616666160408145741] [PMID: 27055579]
[110]
Andritsos, L.A.; Johnson, A.J.; Lozanski, G.; Blum, W.; Kefauver, C.; Awan, F.; Smith, L.L.; Lapalombella, R.; May, S.E.; Raymond, C.A.; Wang, D.S.; Knight, R.D.; Ruppert, A.S.; Lehman, A.; Jarjoura, D.; Chen, C.S.; Byrd, J.C. Higher doses of lenalidomide are associated with unacceptable toxicity including life-threatening tumor flare in patients with chronic lymphocytic leukemia. J. Clin. Oncol., 2008, 26(15), 2519-2525.
[http://dx.doi.org/10.1200/JCO.2007.13.9709] [PMID: 18427150]
[111]
Fecteau, J.F.; Corral, L.G.; Ghia, E.M.; Gaidarova, S.; Futalan, D.; Bharati, I.S.; Cathers, B.; Schwaederlé, M.; Cui, B.; Lopez-Girona, A.; Messmer, D.; Kipps, T.J. Lenalidomide inhibits the proliferation of CLL cells via a cereblon/p21(WAF1/Cip1)-dependent mechanism independent of functional p53. Blood, 2014, 124(10), 1637-1644.
[http://dx.doi.org/10.1182/blood-2014-03-559591] [PMID: 24990888]
[112]
Lopez-Girona, A.; Mendy, D.; Ito, T.; Miller, K.; Gandhi, A.K.; Kang, J.; Karasawa, S.; Carmel, G.; Jackson, P.; Abbasian, M.; Mahmoudi, A.; Cathers, B.; Rychak, E.; Gaidarova, S.; Chen, R.; Schafer, P.H.; Handa, H.; Daniel, T.O.; Evans, J.F.; Chopra, R. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia, 2012, 26(11), 2326-2335.
[http://dx.doi.org/10.1038/leu.2012.119] [PMID: 22552008]
[113]
Görgün, G.; Calabrese, E.; Soydan, E.; Hideshima, T.; Perrone, G.; Bandi, M.; Cirstea, D.; Santo, L.; Hu, Y.; Tai, Y.T.; Nahar, S.; Mimura, N.; Fabre, C.; Raje, N.; Munshi, N.; Richardson, P.; Anderson, K.C. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood, 2010, 116(17), 3227-3237.
[http://dx.doi.org/10.1182/blood-2010-04-279893] [PMID: 20651070]
[114]
Xu, Y.; Li, J.; Ferguson, G.D.; Mercurio, F.; Khambatta, G.; Morrison, L.; Lopez-Girona, A.; Corral, L.G.; Webb, D.R.; Bennett, B.L.; Xie, W. Immunomodulatory drugs reorganize cytoskeleton by modulating Rho GTPases. Blood, 2009, 114(2), 338-345.
[http://dx.doi.org/10.1182/blood-2009-02-200543] [PMID: 19417207]
[115]
Galustian, C.; Meyer, B.; Labarthe, M.C.; Dredge, K.; Klaschka, D.; Henry, J.; Todryk, S.; Chen, R.; Muller, G.; Stirling, D.; Schafer, P.; Bartlett, J.B.; Dalgleish, A.G. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol. Immunother., 2009, 58(7), 1033-1045.
[http://dx.doi.org/10.1007/s00262-008-0620-4] [PMID: 19009291]
[116]
Gaidarova, S.L.J.; Corral, L.G.; Glezer, E.; Schafer, P.H.; Xie, W.; Lopez-Girona, A.; Cheson, B.; Bennett, B. Lenalidomide alone and in combination with rituximab enhances NK cell immune synapse formation in chronic lymphocytic leukemia (CLL) cells in vitro through activation of Rho and Rac1 GTPases. Blood, 2009, 114(22), 3441.
[117]
Ramsay, A.G.; Evans, R.; Kiaii, S.; Svensson, L.; Hogg, N.; Gribben, J.G. Chronic lymphocytic leukemia cells induce defective LFA-1-directed T-cell motility by altering Rho GTPase signaling that is reversible with lenalidomide. Blood, 2013, 121(14), 2704-2714.
[http://dx.doi.org/10.1182/blood-2012-08-448332] [PMID: 23325833]
[118]
Lapalombella, R.; Andritsos, L.; Liu, Q.; May, S.E.; Browning, R.; Pham, L.V.; Blum, K.A.; Blum, W.; Ramanunni, A.; Raymond, C.A.; Smith, L.L.; Lehman, A.; Mo, X.; Jarjoura, D.; Chen, C.S.; Ford, R., Jr; Rader, C.; Muthusamy, N.; Johnson, A.J.; Byrd, J.C. Lenalidomide treatment promotes CD154 expression on CLL cells and enhances production of antibodies by normal B cells through a PI3-kinase-dependent pathway. Blood, 2010, 115(13), 2619-2629.
[http://dx.doi.org/10.1182/blood-2009-09-242438] [PMID: 19965642]
[119]
Fiorcari, S.; Martinelli, S.; Bulgarelli, J.; Audrito, V.; Zucchini, P.; Colaci, E.; Potenza, L.; Narni, F.; Luppi, M.; Deaglio, S.; Marasca, R.; Maffei, R. Lenalidomide interferes with tumor-promoting properties of nurse-like cells in chronic lymphocytic leukemia. Haematologica, 2015, 100(2), 253-262.
[http://dx.doi.org/10.3324/haematol.2014.113217] [PMID: 25398834]
[120]
Maffei, R.; Fiorcari, S.; Bulgarelli, J.; Rizzotto, L.; Martinelli, S.; Rigolin, G.M.; Debbia, G.; Castelli, I.; Bonacorsi, G.; Santachiara, R.; Forconi, F.; Rossi, D.; Laurenti, L.; Palumbo, G.A.; Vallisa, D.; Cuneo, A.; Gaidano, G.; Luppi, M.; Marasca, R. Endothelium-mediated survival of leukemic cells and angiogenesis-related factors are affected by lenalidomide treatment in chronic lymphocytic leukemia. Exp. Hematol, 2014, 42(2), 126-36, e1.
[http://dx.doi.org/10.1016/j.exphem.2013.10.007] [PMID: 24212063]
[121]
Ramsay, A.G.; Johnson, A.J.; Lee, A.M.; Gorgün, G.; Le Dieu, R.; Blum, W.; Byrd, J.C.; Gribben, J.G. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J. Clin. Invest., 2008, 118(7), 2427-2437.
[http://dx.doi.org/10.1172/JCI35017] [PMID: 18551193]
[122]
Shanafelt, T.D.; Ramsay, A.G.; Zent, C.S.; Leis, J.F.; Tun, H.W.; Call, T.G.; LaPlant, B.; Bowen, D.; Pettinger, A.; Jelinek, D.F.; Hanson, C.A.; Kay, N.E. Long-term repair of T-cell synapse activity in a phase II trial of chemoimmunotherapy followed by lenalidomide consolidation in previously untreated chronic lymphocytic leukemia (CLL). Blood, 2013, 121(20), 4137-4141.
[http://dx.doi.org/10.1182/blood-2012-12-470005] [PMID: 23493782]
[123]
Noonan, K.; Rudraraju, L.; Ferguson, A.; Emerling, A.; Pasetti, M.F.; Huff, C.A.; Borrello, I. Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. Clin. Cancer Res., 2012, 18(5), 1426-1434.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1221]
[124]
Ehninger, A.; Trumpp, A. The bone marrow stem cell niche grows up: Mesenchymal stem cells and macrophages move in. J. Exp. Med., 2011, 208(3), 421-428.
[http://dx.doi.org/10.1084/jem.20110132] [PMID: 21402747]
[125]
Blazar, B.R.; Carreno, B.M.; Panoskaltsis-Mortari, A.; Carter, L.; Iwai, Y.; Yagita, H.; Nishimura, H.; Taylor, P.A. Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism. J. Immunol., 2003, 171(3), 1272-1277.
[http://dx.doi.org/10.4049/jimmunol.171.3.1272] [PMID: 12874215]
[126]
Fenaux, P.; Mufti, G.J.; Hellstrom-Lindberg, E.; Santini, V.; Finelli, C.; Giagounidis, A.; Schoch, R.; Gattermann, N.; Sanz, G.; List, A.; Gore, S.D.; Seymour, J.F.; Bennett, J.M.; Byrd, J.; Backstrom, J.; Zimmerman, L.; McKenzie, D.; Beach, C.; Silverman, L.R. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol., 2009, 10(3), 223-232.
[http://dx.doi.org/10.1016/S1470-2045(09)70003-8] [PMID: 19230772]
[127]
Kantarjian, H.M.; Thomas, X.G.; Dmoszynska, A.; Wierzbowska, A.; Mazur, G.; Mayer, J.; Gau, J.P.; Chou, W.C.; Buckstein, R.; Cermak, J.; Kuo, C.Y.; Oriol, A.; Ravandi, F.; Faderl, S.; Delaunay, J.; Lysák, D.; Minden, M.; Arthur, C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J. Clin. Oncol., 2012, 30(21), 2670-2677.
[http://dx.doi.org/10.1200/JCO.2011.38.9429] [PMID: 22689805]
[128]
Larocca, A.; Mina, R.; Gay, F.; Bringhen, S.; Boccadoro, M. Emerging drugs and combinations to treat multiple myeloma. Oncotarget, 2017, 8(36), 60656-60672.
[http://dx.doi.org/10.18632/oncotarget.19269] [PMID: 28948001]
[129]
Tvedt, T.H.; Nepstad, I.; Bruserud, Ø. Antileukemic effects of midostaurin in acute myeloid leukemia - the possible importance of multikinase inhibition in leukemic as well as nonleukemic stromal cells. Expert Opin. Investig. Drugs, 2017, 26(3), 343-355.
[http://dx.doi.org/10.1080/13543784.2017.1275564] [PMID: 28001095]
[130]
Lecciso, M.; Ocadlikova, D.; Sangaletti, S.; Trabanelli, S.; De Marchi, E.; Orioli, E.; Pegoraro, A.; Portararo, P.; Jandus, C.; Bontadini, A.; Redavid, A.; Salvestrini, V.; Romero, P.; Colombo, M.P.; Di Virgilio, F.; Cavo, M.; Adinolfi, E.; Curti, A. ATP release from chemotherapy-treated dying leukemia cells elicits an immune suppressive effect by increasing regulatory T cells and tolerogenic dendritic cells. Front. Immunol., 2017, 8, 1918.
[http://dx.doi.org/10.3389/fimmu.2017.01918] [PMID: 29312358]
[131]
Wątek, M.; Durnaś, B.; Wollny, T.; Pasiarski, M.; Góźdź, S.; Marzec, M.; Chabowska, A.; Wolak, P.; Żendzian-Piotrowska, M.; Bucki, R. Unexpected profile of sphingolipid contents in blood and bone marrow plasma collected from patients diagnosed with acute myeloid leukemia. Lipids Health Dis., 2017, 16(1), 235.
[http://dx.doi.org/10.1186/s12944-017-0624-1] [PMID: 29216917]
[132]
Rodriguez, Y.I.; Campos, L.E.; Castro, M.G.; Aladhami, A.; Oskeritzian, C.A.; Alvarez, S.E. Sphingosine-1 phosphate: A new modulator of immune plasticity in the tumor microenvironment. Front. Oncol., 2016, 6, 218.
[http://dx.doi.org/10.3389/fonc.2016.00218] [PMID: 27800303]
[133]
Powell, J.A.; Lewis, A.C.; Zhu, W.; Toubia, J.; Pitman, M.R.; Wallington-Beddoe, C.T.; Moretti, P.A.; Iarossi, D.; Samaraweera, S.E.; Cummings, N.; Ramshaw, H.S.; Thomas, D.; Wei, A.H.; Lopez, A.F.; D’Andrea, R.J.; Lewis, I.D.; Pitson, S.M. Targeting sphingosine kinase 1 induces MCL1-dependent cell death in acute myeloid leukemia. Blood, 2017, 129(6), 771-782.
[http://dx.doi.org/10.1182/blood-2016-06-720433] [PMID: 27956387]

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