Targeting immune checkpoints in hematologic malignancies

Pharmacological Reviews

Volumn 68, Issue 4, 2016, Pages 1014-1025

  Alatrash, Gheath ^a   Daver, Naval ^b   Mittendorf, Elizabeth A ^b  

^a Departments of Stem Cell Transplantation and Cellular Therapy   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC MONOCLONAL ANTIBODY; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; MONOCLONAL ANTIBODY;

ALLOGENEIC STEM CELL TRANSPLANTATION; BONE MARROW; CANCER IMMUNOTHERAPY; CELL LINEAGE; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; LYMPH NODE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; SOLID MALIGNANT NEOPLASM; SYSTEMATIC REVIEW; GENETICS; HEMATOLOGIC DISEASE; IMMUNOTHERAPY; LUNG TUMOR; NON SMALL CELL LUNG CANCER;

ANTIBODIES, MONOCLONAL; B7-H1 ANTIGEN; CARCINOMA, NON-SMALL-CELL LUNG; CTLA-4 ANTIGEN; HEMATOLOGIC NEOPLASMS; HUMANS; IMMUNOTHERAPY; LUNG NEOPLASMS;

EID: 85011046277     PISSN: 00316997     EISSN: 15210081     Source Type: Journal    
DOI: 10.1124/pr.116.012682     Document Type: Review

References (84)

1. Alho AC, Kim HT, Chammas MJ, Reynolds CG, Matos TR, Forcade E, Whangbo J, Nikiforow S, Cutler CS, Koreth J, et al. (2016) Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD. Blood 127:646-657.
2. Andorsky DJ, Yamada RE, Said J, Pinkus GS, Betting DJ, and Timmerman JM (2011) Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res 17:4232-4244
3. Angenendt L, Schliemann C, Lutz M, Rebber E, Schulze AB, Weckesser M, Stegger L, Schäfers M, Groth C, Kessler T, et al. (2016) Nivolumab in a patient with refractory Hodgkin’s lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant 51:443-445.
4. Ankri C, Shamalov K, Horovitz-Fried M, Mauer S, and Cohen CJ (2013) Human T cells engineered to express a programmed death 1/28 costimulatory retargeting molecule display enhanced antitumor activity. J Immunol 191:4121-4129
5. Ansell S, Armand P, Timmerman JM, Shipp MA, Bradley-Garelik MB, Zhu L, and Lesokhin AM (2015a) Nivolumab in Patients (Pts) with relapsed or refractory classical Hodgkin lymphoma (R/R cHL): Clinical outcomes from extended follow-up of a phase 1 study (CA209-039), in American Society of Hematology Annual Meeting; 2015 December 5-12; Orlando, FL. Abstract 583, American Society of Hematology, Washington, D.C.
6. Ansell SM, Hurvitz SA, Koenig PA, LaPlant BR, Kabat BF, Fernando D, Habermann TM, Inwards DJ, Verma M, Yamada R, et al. (2009) Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res 15:6446-6453.
7. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, et al. (2015b) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311-319
8. Ansell SM, Stenson M, Habermann TM, Jelinek DF, and Witzig TE (2001) Cd4+ T-cell immune response to large B-cell non-Hodgkin’s lymphoma predicts patient outcome. J Clin Oncol 19:720-726.
9. Armand P, Nagler A, Weller EA, Devine SM, Avigan DE, Chen YB, Kaminski MS, Holland HK, Winter JN, Mason JR, et al. (2013) 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 31:4199-4206.
10. Atanackovic D, Arfsten J, Cao Y, Gnjatic S, Schnieders F, Bartels K, Schilling G, Faltz C, Wolschke C, Dierlamm J, et al. (2007) Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Blood 109:1103-1112.
11. Bashey A, Medina B, Corringham S, Pasek M, Carrier E, Vrooman L, Lowy I, Solomon SR, Morris LE, Holland HK, et al. (2009) CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood 113:1581-1588.
12. Bensinger WI, Maloney D, and Storb R (2001) Allogeneic hematopoietic cell transplantation for multiple myeloma. Semin Hematol 38:243-249.
13. Berger R, Rotem-Yehudar R, Slama G, Landes S, Kneller A, Leiba M, KorenMichowitz M, Shimoni A, and Nagler A (2008) 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 14:3044-3051.
14. Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Musto P, Beksac M, Bosi A, et al. (2011) Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol 29:3016-3022.
15. Bladé J, Rosiñol L, Cibeira MT, Rovira M, and Carreras E (2010) Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. Blood 115:3655-3663
16. Blazar BR, Taylor PA, Boyer MW, Panoskaltsis-Mortari A, Allison JP, and Vallera DA (1997) CD28/B7 interactions are required for sustaining the graft-versusleukemia effect of delayed post-bone marrow transplantation splenocyte infusion in murine recipients of myeloid or lymphoid leukemia cells. J Immunol 159: 3460-3473.
17. Blazar BR, Taylor PA, Linsley PS, and Vallera DA (1994) In vivo blockade of CD28/CTLA4: B7/BB1 interaction with CTLA4-Ig reduces lethal murine graft-versus-host disease across the major histocompatibility complex barrier in mice. Blood 83:3815-3825.
18. Blazar BR, Taylor PA, Panoskaltsis-Mortari A, Gray GS, and Vallera DA (1995) Coblockade of the LFA1:ICAM and CD28/CTLA4:B7 pathways is a highly effective means of preventing acute lethal graft-versus-host disease induced by fully major histocompatibility complex-disparate donor grafts. Blood 85:2607-2618.
19. Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omedè P, Baldi I, et al. (2007) A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 356:1110-1120
20. Chaperot L, Plumas J, Jacob MC, Bost F, Molens JP, Sotto JJ, and Bensa JC (1999) Functional expression of CD80 and CD86 allows immunogenicity of malignant B cells from non-Hodgkin’s lymphomas. Exp Hematol 27:479-488.
21. Chung DJ, Pronschinske KB, Shyer JA, Sharma S, Leung S, Curran SA, Lesokhin AM, Devlin SM, Giralt SA, and Young JW (2016) T-cell Exhaustion in Multiple Myeloma Relapse after Autotransplant: Optimal Timing of Immunotherapy. Cancer Immunol Res 4:61-71.
22. Costello RT, Mallet F, Sainty D, Maraninchi D, Gastaut JA, and Olive D (1998) 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 28:90-103.
23. Couzin-Frankel J (2013) Breakthrough of the year 2013. Cancer immunotherapy. Science 342:1432-1433.
24. Daver N, Basu S, Garcia-Manero G, Cortes J, Ravandi F, Kornblau S, Konopleva M, Andreeff M, Borthakur G, Jain N, et al. (2016) Defining the immune checkpoint landscape of acute myeloid leukemia (AML), in American Association for Cancer Research Annual Meeting; 2016 April 16-20; New Orleans, LA. American Association for Cancer Research, Philadelphia.
25. Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, et al.; Leukemia and Lymphoma Society Blood Cancer Research Partnership (2016) Ipilimumab for Patients with Relapse after Allogeneic Transplantation. N Engl J Med 375:143-153.
26. Dizon DS, Krilov L, Cohen E, Gangadhar T, Ganz PA, Hensing TA, Hunger S, Krishnamurthi SS, Lassman AB, Markham MJ, et al. (2016) Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. J Clin Oncol 34:987-1011.
27. Dorfman DM, Schultze JL, Shahsafaei A, Michalak S, Gribben JG, Freeman GJ, Pinkus GS, and Nadler LM (1997) In vivo expression of B7-1 and B7-2 by follicular lymphoma cells can prevent induction of T-cell anergy but is insufficient to induce significant T-cell proliferation. Blood 90:4297-4306.
28. Dutt S, Tseng D, Ermann J, George TI, Liu YP, Davis CR, Fathman CG, and Strober S (2007) Naive and memory T cells induce different types of graft-versus-host disease. J Immunol 179:6547-6554.
29. Egen JG and Allison JP (2002) Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity 16:23-35
30. Fevery S, Billiau AD, Sprangers B, Rutgeerts O, Lenaerts C, Goebels J, Landuyt W, Kasran A, Boon L, Sagaert X, et al. (2007) CTLA-4 blockade in murine bone marrow chimeras induces a host-derived antileukemic effect without graft-versus-host disease. Leukemia 21:1451-1459.
31. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, and Sharpe AH (2009) PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 206:3015-3029
32. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, et al. (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027-1034.
33. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al.; KEYNOTE-001 Investigators (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372: 2018-2028.
34. Görgün G, Samur MK, Cowens KB, Paula S, Bianchi G, Anderson JE, White RE, Singh A, Ohguchi H, Suzuki R, et al. (2015) Lenalidomide enhances immune checkpoint blockade-induced immune response in multiple myeloma. Clin Cancer Res 21:4607-4618.
35. Graf M, Reif S, Hecht K, Pelka-Fleischer R, Kroell T, Pfister K, and Schmetzer H (2005) High expression of costimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML). Ann Hematol 84:287-297
36. Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O’Donnell E, Chapuy B, Takeyama K, Neuberg D, Golub TR, et al. (2010) 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 116:3268-3277.
37. Green MR, Rodig S, Juszczynski P, Ouyang J, Sinha P, O’Donnell E, Neuberg D, and Shipp MA (2012) Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res 18:1611-1618.
38. Grogan TM and Miller TP (1993) Immunobiologic correlates of prognosis in lymphoma. Semin Oncol 20(5, Suppl 5) 58-74.
39. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, et al. (2013) Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368:1509-1518
40. Guillaume T, Rubinstein DB, and Symann M (1998) Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation. Blood 92:1471-1490.
41. John LB, Devaud C, Duong CP, Yong CS, Beavis PA, Haynes NM, Chow MT, Smyth MJ, Kershaw MH, and Darcy PK (2013) Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 19:5636-5646.
42. Koestner W, Hapke M, Herbst J, Klein C, Welte K, Fruehauf J, Flatley A, Vignali DA, Hardtke-Wolenski M, Jaeckel E, et al. (2011) PD-L1 blockade effectively restores strong graft-versus-leukemia effects without graft-versus-host disease after delayed adoptive transfer of T-cell receptor gene-engineered allogeneic CD8+ T cells. Blood 117:1030-1041.
43. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. (2015) Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 373:23-34
44. Leach DR, Krummel MF, and Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734-1736.
45. Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, Millenson MM, Cohen AD, Schuster SJ, Lebovic D, et al. (2014) Preliminary results of a phase I study of Nivolumab (BMS-936558) in patients with relapsed or refractory lymphoid malignancies, in American Society of Hematology Annual Meeting; 2014 December 6-9; San Francisco, CA. Abstract 291, American Society of Hematology, Washington, D.C.
46. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, and Peach R (1994) Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1:793-801.
47. Lippman SM, Spier CM, Miller TP, Slymen DJ, Rybski JA, and Grogan TM (1990) Tumor-infiltrating T-lymphocytes in B-cell diffuse large cell lymphoma related to disease course. Mod Pathol 3:361-367.
48. Maude SL, Teachey DT, Porter DL, and Grupp SA (2015) CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood 125: 4017-4023.
49. McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, JamalHanjani M, Wilson GA, Birkbak NJ, Hiley CT, et al. (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351:1463-1469.
50. Mehta J and Singhal S (1998) Graft-versus-myeloma. Bone Marrow Transplant 22: 835-843.
51. Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE, and Davis MM (2000) Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 6:1018-1023.
52. Moskowitz C, Ribrag V, Michot JM, Martinelli G, Zinzani PL, Gutierrez M, De Maeyer G, Jacob AG, Giallella K, Anderson JW, et al. (2014) 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), in American Society of Hematology Annual Meeting; 2014 December 6-9; San Francisco, CA. Abstract 290, American Society of Hematology, Washington, D.C.
53. Mumprecht S, Schürch C, Schwaller J, Solenthaler M, and Ochsenbein AF (2009) Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression. Blood 114:1528-1536
54. Nishimura H, Nose M, Hiai H, Minato N, and Honjo T (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motifcarrying immunoreceptor. Immunity 11:141-151.
55. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, et al. (2001) Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291:319-322.
56. Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, et al. (2015) Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 7:303ra139.
57. Porter DL, Levine BL, Kalos M, Bagg A, and June CH (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365: 725-733.
58. Ray A, Das DS, Song Y, Richardson P, Munshi NC, Chauhan D, and Anderson KC (2015) Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cell interactions with T cells, natural killer cells and multiple myeloma cells. Leukemia 29:1441-1444.
59. Re F, Arpinati M, Testoni N, Ricci P, Terragna C, Preda P, Ruggeri D, Senese B, Chirumbolo G, Martelli V, et al. (2002) Expression of CD86 in acute myelogenous leukemia is a marker of dendritic/monocytic lineage. Exp Hematol 30:126-134
60. Riley JL, Mao M, Kobayashi S, Biery M, Burchard J, Cavet G, Gregson BP, June CH, and Linsley PS (2002) Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc Natl Acad Sci USA 99: 11790-11795.
61. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al. (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348: 124-128.
62. Roddie C and Peggs KS (2011) Donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation. Expert Opin Biol Ther 11:473-487.
63. Rudd CE, Taylor A, and Schneider H (2009) CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol Rev 229:12-26.
64. Saha A, Aoyama K, Taylor PA, Koehn BH, Veenstra RG, Panoskaltsis-Mortari A, Munn DH, Murphy WJ, Azuma M, Yagita H, et al. (2013) Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality. Blood 122:3062-3073.
65. San Miguel J, Mateos M, Shah JJ, Ocio EM, Rodriguez-Otero P, Reece D, Munshi NC, Avigan DE, Ge Y, Balakumaran A, et al. (2015) Pembrolizumab in combination with lenalidomide and low-dose dexamethasone for relapsed/refractory multiple myeloma (RRMM): Keynote-023, in American Society of Hematology Annual Meeting; 2015 December 5-8; Orlando, FL. Abstract 505, American Society of Hematology, Washington, D.C.
66. Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, Wei B, Hogg N, Garside P, and Rudd CE (2006) Reversal of the TCR stop signal by CTLA-4. Science 313:1972-1975.
67. Shin JH, Park HB, Oh YM, Lim DP, Lee JE, Seo HH, Lee SJ, Eom HS, Kim IH, Lee SH, et al. (2012) Positive conversion of negative signaling of CTLA4 potentiates antitumor efficacy of adoptive T-cell therapy in murine tumor models. Blood 119:5678-5687
68. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, et al. (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371:2189-2199.
69. Suen H, Brown R, Yang S, Ho PJ, Gibson J, and Joshua D (2015) The failure of immune checkpoint blockade in multiple myeloma with PD-1 inhibitors in a phase 1 study. Leukemia 29:1621-1622.
70. Suen H, Joshua DE, Brown RD, Yang S, Barbaro PM, Ho PJ, and Gibson J (2014) Protective cytotoxic clonal T-cells in myeloma have the characteristics of telomere-independent senescence rather than an exhausted or anergic phenotype: Implications for immunotherapy, in American Society of Hematology Annual Meeting; 2014 December 6-9; San Francisco, CA. pp 3367, American Society of Hematology, Washington, D.C
71. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, and Anders RA (2014) Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 20:5064-5074.
72. Tchekmedyian S, Glaspy J, Korman A, Keler T, Deo Y, and Davis T (2002) MDX-010 (human anti-CTLA4): a phase I trial in malignant melanoma, in Proceedings of the American Society of Clinical Oncology; 2002 May 18-21; Orlando, FL. Abstract 56, American Society of Clinical Oncology, Alexandria, VA.
73. Tsukada N, Aoki S, Maruyama S, Kishi K, Takahashi M, and Aizawa Y (1997) The heterogeneous expression of CD80, CD86 and other adhesion molecules on leukemia and lymphoma cells and their induction by interferon. J Exp Clin Cancer Res 16:171-176
74. Tyler EM, Jungbluth AA, O’Reilly RJ, and Koehne G (2013) WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing allogeneic T celldepleted hematopoietic stem cell transplantation and donor lymphocyte infusions. Blood 121:308-317.
75. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, Sucker A, Hillen U, Geukes Foppen MH, Goldinger SM, et al. (2015) Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350:207-211
76. Vollmer M, Li L, Schmitt A, Greiner J, Reinhardt P, Ringhoffer M, Wiesneth M, Döhner H, and Schmitt M (2003) Expression of human leucocyte antigens and co-stimulatory molecules on blasts of patients with acute myeloid leukaemia. Br J Haematol 120:1000-1008.
77. Westin JR, Chu F, Zhang M, Fayad LE, Kwak LW, Fowler N, Romaguera J, Hagemeister F, Fanale M, Samaniego F, et al. (2014) 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 15: 69-77.
78. Whiteway A, Corbett T, Anderson R, Macdonald I, and Prentice HG (2003) Expression of co-stimulatory molecules on acute myeloid leukaemia blasts may effect duration of first remission. Br J Haematol 120:442-451.
79. Wrangle J, Wang W, Koch A, Easwaran H, Mohammad HP, Vendetti F, Vancriekinge W, Demeyer T, Du Z, Parsana P, et al. (2013) Alterations of immune response of Non-Small Cell Lung Cancer with Azacytidine. Oncotarget 4:2067-2079.
80. Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, Fang Z, Nguyen M, Pierce S, Wei Y, et al. (2014) Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia 28:1280-1288.
81. Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, and Saito T (2012) Programmed cell death 1 forms negative costimulatory micro-clusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med 209:1201-1217.
82. Zhang M, Xiao XQ, Jiang YF, Liang YS, Peng MY, Xu Y, and Gong GZ (2011) DNA demethylation in PD-1 gene promoter induced by 5-azacytidine activates PD-1 expression on Molt-4 cells. Cell Immunol 271:450-454.
83. Zheng H, Matte-Martone C, Jain D, McNiff J, and Shlomchik WD (2009) Central memory CD8+ T cells induce graft-versus-host disease and mediate graft-versus-leukemia. J Immunol 182:5938-5948.
84. Zhou Q, Munger ME, Highfill SL, Tolar J, Weigel BJ, Riddle M, Sharpe AH, Vallera DA, Azuma M, Levine BL, et al. (2010) 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 116: 2484-2493