The emerging role of immune checkpoint based approaches in AML and MDS

Leukemia and Lymphoma

Volumn 59, Issue 4, 2018, Pages 790-802

  Boddu, Prajwal ^a   Kantarjian, Hagop ^a   Garcia Manero, Guillermo ^a   Allison, James ^a   Sharma, Padmanee ^a   Daver, Naval ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

Acute myeloid leukemia; Checkpoint inhibitors; Immunotherapy; Myelodysplastic syndrome

Indexed keywords

ANTINEOPLASTIC MONOCLONAL ANTIBODY; AZACITIDINE; CYTOTOXIC AGENT; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; IMMUNE CHECKPOINT INHIBITOR; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 LIGAND 2; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; IMMUNOLOGICAL ANTINEOPLASTIC AGENT; T LYMPHOCYTE RECEPTOR;

ACUTE MYELOID LEUKEMIA; ALLOGENEIC STEM CELL TRANSPLANTATION; GENETIC ASSOCIATION; GRAFT VERSUS HOST REACTION; HEMATOLOGIC MALIGNANCY; HUMAN; MINIMAL RESIDUAL DISEASE; MYELODYSPLASTIC SYNDROME; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; UPREGULATION; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); DNA METHYLATION; DRUG EFFECT; DRUG RESISTANCE; IMMUNOLOGY; METABOLISM; PATHOLOGY; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS AS TOPIC; COSTIMULATORY AND INHIBITORY T-CELL RECEPTORS; DNA METHYLATION; DRUG RESISTANCE, NEOPLASM; HUMANS; LEUKEMIA, MYELOID, ACUTE; MYELODYSPLASTIC SYNDROMES; T-LYMPHOCYTES; TREATMENT OUTCOME; UP-REGULATION;

EID: 85022039320     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.1080/10428194.2017.1344905     Document Type: Review

References (85)

1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12: 252–264.
2. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8:467–477.
3. Chen L, Flies DB. Molecular mechanisms of T cell costimulation and co-inhibition. Nat Rev Immunol. 2013;13:227–242.
4. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–1736.
5. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723.
6. O'Day SJ, Maio M, Chiarion-Sileni V, et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Ann Oncol. 2010;21:1712–1717.
7. Sui X, Ma J, Han W, et al. The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of response to anti-PD-1/PD-L1 antibodies in cancer patients. Oncotarget. 2015;6:19393–19404.
8. Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291:319–322.
9. Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11:141–151.
10. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027–1034.
11. Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 2012;209:1201–1217.
12. Alatrash G, Daver N, Mittendorf EA. Targeting immune checkpoints in hematologic malignancies. Pharmacol Rev. 2016;68:1014–1025.
13. Costello RT, Mallet F, Sainty D, et al. Regulation of CD80/B7-1 and CD86/B7-2 molecule expression in human primary acute myeloid leukemia and their role in allogenic immune recognition. Eur J Immunol. 1998;28:90–103.
14. Re F, Arpinati M, Testoni N, et al. Expression of CD86 in acute myelogenous leukemia is a marker of dendritic/monocytic lineage. Exp Hematol. 2002;30: 126–134.
15. Vollmer M, Li L, Schmitt A, et al. Expression of human leucocyte antigens and co-stimulatory molecules on blasts of patients with acute myeloid leukaemia. Br J Haematol. 2003;120:1000–1008.
16. Whiteway A, Corbett T, Anderson R, et al. Expression of co-stimulatory molecules on acute myeloid leukaemia blasts may effect duration of first remission. Br J Haematol. 2003;120:442–451.
17. Graf M, Reif S, Hecht K, et al. High expression of costimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML). Ann Hematol. 2005;84:287–297.
18. Zhang L, Chen X, Liu X, et al. CD40 ligation reverses T cell tolerance in acute myeloid leukemia. J Clin Invest. 2013;123:1999–2010.
19. Teague RM, Kline J. Immune evasion in acute myeloid leukemia: current concepts and future directions. J Immunother Cancer. 2013;1:13.
20. Vidriales MB, Orfao A, López-Berges MC, et al. Lymphoid subsets in acute myeloid leukemias: increased number of cells with NK phenotype and normal T-cell distribution. Ann Hematol. 1993;67: 217–222.
21. Naval Daver SB, Garcia-Manero G, Cortes JE, et al. Defining the immune checkpoint landscape in patients (pts) with acute myeloid leukemia. ASH Session. 2016;617:abstract 2900.
22. Le Dieu R, Taussig DC, Ramsay AG, et al. Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts. Blood. 2009;114:3909–3916.
23. Van den Hove LE, Vandenberghe P, Van Gool SW, et al. Peripheral blood lymphocyte subset shifts in patients with untreated hematological tumors: evidence for systemic activation of the T cell compartment. Leuk Res. 1998;22:175–184.
24. Schnorfeil FM, Lichtenegger FS, Emmerig K, et al. 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.
25. Wendelbo O, Nesthus I, Sjo M, et al. Functional characterization of T lymphocytes derived from patients with acute myelogenous leukemia and chemotherapy-induced leukopenia. Cancer Immunol Immunother. 2004;53:740–747.
26. Adam Lamble YK, Huang F, Sasser K, et al. Mass cytometry as a modality to identify candidates for immune checkpoint inhibitor therapy within acute myeloid leukemia. ASH Abstract #2829; 2016.
27. Page DB, Postow MA, Callahan MK, et al. Immune modulation in cancer with antibodies. Annu Rev Med. 2014;65:185–202.
28. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–2526.
29. Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116: 3268–3277.
30. Green MR, Rodig S, Juszczynski P, et al. Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res. 2012;18:1611–1618.
31. Ansell SM, Iwamoto FM, LaCasce A, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372: 311–319.
32. Moskowitz C, Ribrag V, Michot JM, et al. PD-1 blockade with the monoclonal antibody pembrolizumab (MK-3475) in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: preliminary results from a phase 1b study (KEYNOTE-013). 56th ASH Annual Meeting and Exposition; 2014; San Francisco, CA.
33. Berger R, Rotem-Yehudar R, Slama G, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res. 2008;14:3044–3051.
34. Westin JR, Chu F, Zhang M, et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol. 2014;15:69–77.
35. Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013;31:4199–4206.
36. Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. JCO. 2016;34:2698–2704.
37. San Miguel J, Siegel D, Shah JJ, et al. Pembrolizumab in combination with lenalidomide and low-dose dexamethasone for relapsed/refractory multiple myeloma (RRMM): keynote-023. American Society of Hematology Annual Meeting; 2015.
38. Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood. 2009;114: 1545–1552.
39. Zhou Q, Munger ME, Veenstra RG, et al. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood. 2011;117:4501–4510.
40. Daver N, et al. Defining the immune checkpoint landscape in patients (pts) with acute myeloid leukemia (AML). Blood. 2016;128:abstract 2900.
41. Mumprecht S, Schürch C, Schwaller J, et al. Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression. Blood. 2009;114:1528–1536.
42. Shi L, Chen S, Yang L, et al. The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol. 2013;6:74.
43. Chen X, Liu S, Wang L, et al. Clinical significance of B7-H1 (PD-L1) expression in human acute leukemia. Cancer Biol Ther. 2008;7:622–627.
44. Fourcade J, Sun Z, Benallaoua M, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med. 2010;207:2175–2186.
45. Zhou Q, Munger ME, Highfill SL, et al. 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;116:2484–2493.
46. Dolen Y, Esendagli G. Myeloid leukemia cells with a B7-2(+) subpopulation provoke Th-cell responses and become immuno-suppressive through the modulation of B7 ligands. Eur J Immunol. 2013;43:747–757.
47. Marketwired U.S. FDA Lifts Partial Clinical Hold on Medivation's Pidilizumab. March 9; 2016.
48. Garcia-Manero G, Tallman MS, Martinelli G, et al. Pembrolizumab, a PD-1 inhibitor, in Patients with Myelodysplastic Syndrome (MDS) after Failure of Hypomethylating Agent Treatment. American Society of Hematology, Dec 2016 (abstract); 2016.
49. Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108:419–425.
50. Riley JL, Mao M, Kobayashi S, et al. Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc Natl Acad Sci USA. 2002;99:11790–11795.
51. Linsley PS, Greene JL, Brady W, et al. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity. 1994;1:793–801.
52. Schneider H, Downey J, Smith A, et al. Reversal of the TCR stop signal by CTLA-4. Science. 2006;313: 1972–1975.
53. Egen JG, Allison JP. Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity. 2002;16: 23–35.
54. Saudemont A, Quesnel B. In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis. Blood. 2004;104:2124–2133.
55. Laurent S, Palmisano GL, Martelli AM, et al. CTLA-4 expressed by chemoresistant, as well as untreated, myeloid leukaemia cells can be targeted with ligands to induce apoptosis. Br J Haematol. 2007;136:597–608.
56. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366:2517–2519.
57. Zeidan AM, Kharfan-Dabaja MA, Komrokji RS. Stabilization of myelodysplastic syndromes (MDS) following hypomethylating agent (HMAs) failure using the immune checkpoint inhibitor ipilimumab: a phase I trial. Blood. 2015;126:1666–1666.
58. Wrangle J, Wang W, Koch A, et al. Alterations of immune response of non-small cell lung cancer with azacytidine. Oncotarget. 2013;4:2067–2079.
59. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. 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;10:223–232.
60. Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291–299.
61. Fenaux P, Mufti GJ, Hellström-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28:562–569.
62. Guo H, Miao H, Gerber L, et al. Disruption of EphA2 receptor tyrosine kinase leads to increased susceptibility to carcinogenesis in mouse skin. Cancer Res. 2006;66:7050–7058.
63. Srivastava P, Paluch BE, Matsuzaki J, et al. Induction of cancer testis antigen expression in circulating acute myeloid leukemia blasts following hypomethylating agent monotherapy. Oncotarget. 2016;7:12840–12856.
64. '-deoxycytidine-induced expression of functional cancer testis antigens in human renal cell carcinoma: immunotherapeutic implications. Clin Cancer Res. 2002;8:2690–2695.
65. '-deoxycytidine (5-AZA-CdR). J Immunother. 1999;22:16–24.
66. '-deoxycytidine treatment. Int J Cancer. 2001;94:243–251.
67. Garcia-Manero G, Daver NG, Montalban-Bravo G, et al. A phase II study evaluating the combination of nivolumab or ipilimumab with azacitidine in patients with previously treated or untreated myelodysplastic syndromes. American Society of Hematology, Dec 2016 (oral presentation).
68. Yang H, Bueso-Ramos C, DiNardo C, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2014;28:1280–1288.
69. Naval Daver SBG, Garcia-Manero JE, Cortes F, et al. Phase IB/II study of nivolumab in combination with azacytidine in patients with relapsed acute myeloid leukemia. American Society of Hematology, Dec 2016 (abstract); 2016.
70. Vereecque R, Saudemont A, Quesnel B. Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells. Leukemia. 2004;18: 1223–1230.
71. Saha A, Aoyama K, Taylor PA, et al. Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality. Blood. 2013;122:3062–3073.
72. Blazar BR, Carreno BM, Panoskaltsis-Mortari A, et al. Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism. J Immunol. 2003;171:1272–1277.
73. Blazar BR, et al. Opposing roles of CD28:B7 and CTLA-4:B7 pathways in regulating in vivo alloresponses in murine recipients of MHC disparate T cells. J Immunol. 1999;162:6368–6377.
74. Davids MS, Haesook T, Bachireddy P, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016;375:143–153.
75. Herbaux C, Gauthier J, Brice P, et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin's lymphoma. Blood. 2017;129:2471–2478.
76. Saudemont A, Buffenoir G, Denys A, et al. Gene transfer of CD154 and IL12 cDNA induces an anti-leukemic immunity in a murine model of acute leukemia. Leukemia. 2002;16:1637–1644.
77. Workman CJ, Rice DS, Dugger KJ, et al. Phenotypic analysis of the murine CD4-related glycoprotein, CD223 (LAG-3). Eur J Immunol. 2002;32:2255–2263.
78. Huang CT, Workman CJ, Flies D, et al. Role of LAG-3 in regulatory T cells. Immunity. 2004;21:503–513.
79. Grosso JF, Goldberg MV, Getnet D, et al. Functionally distinct LAG-3 and PD-1 subsets on activated and chronically stimulated CD8 T cells. J Immunol. 2009;182:6659–6669.
80. Berrien-Elliott MM, Jackson SR, Meyer JM, et al. Durable adoptive immunotherapy for leukemia produced by manipulation of multiple regulatory pathways of CD8+ T-cell tolerance. Cancer Res. 2013;73: 605–616.
81. Zhu C, Anderson AC, Schubart A, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6:1245–1252.
82. Wang C, Lin GH, McPherson AJ, et al. Immune regulation by 4-1BB and 4-1BBL: complexities and challenges. Immunol Rev. 2009;229:192–215.
83. Richter G, Hayden-Ledbetter M, Irgang M, et al. Tumor necrosis factor-alpha regulates the expression of inducible costimulator receptor ligand on CD34(+) progenitor cells during differentiation into antigen presenting cells. J Biol Chem. 2001;276:45686–45693.
84. Richter G, Burdach S. ICOS: a new costimulatory ligand/receptor pair and its role in T-cell activation. Onkologie. 2004;27:91–95.
85. Lucia Masarova HK, Daver N. Immune checkpoint approaches in AML and MDS: a next frontier? Target Oncol. 2017 [published online March 06, 2017].