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

Journal of Hematology and Oncology

Volumn 8, Issue 1, 2015, Pages

  Schnorfeil, Frauke M ^a,b   Lichtenegger, Felix S ^a,b   Emmerig, Katharina ^a,b   Schlueter, Miriam ^a,b   Neitz, Julia S ^a,b   Draenert, Rika ^a   Hiddemann, Wolfgang ^a,b   Subklewe, Marion ^a,b  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b German Res Cen for Env Health/Clin Coop Gr Hematopoietic Cell Transplantation (CCG HCT)   (Germany)

Author keywords

Acute myeloid leukemia (AML); Cancer immunotherapy; Immune checkpoint molecules; PD 1; T cell exhaustion

Indexed keywords

ANTIGEN; CD160 ANTIGEN; CD244 ANTIGEN; CD45RA ANTIGEN; CHEMOKINE RECEPTOR CCR7; GAMMA INTERFERON; INTERLEUKIN 2; IONOMYCIN; PHORBOL 13 ACETATE 12 MYRISTATE; PROGRAMMED DEATH 1 RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ACUTE MYELOBLASTIC LEUKEMIA; ADULT; AGE; ALLOGENEIC STEM CELL TRANSPLANTATION; ANTIGEN EXPRESSION; ARTICLE; CANCER IMMUNOTHERAPY; CANCER PATIENT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL FUNCTION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOMEGALOVIRUS; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INTERFERON PRODUCTION; LEUKEMIA RELAPSE; MEMORY CELL; MEMORY T LYMPHOCYTE; PHENOTYPE; PROTEIN EXPRESSION; T LYMPHOCYTE; UPREGULATION; ACUTE MYELOID LEUKEMIA; FEMALE; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; MALE; METABOLISM; PROCEDURES; RECURRENT DISEASE;

CD8-POSITIVE T-LYMPHOCYTES; FEMALE; HUMANS; IMMUNOTHERAPY; LEUKEMIA, MYELOID, ACUTE; MALE; PROGRAMMED CELL DEATH 1 RECEPTOR; RECURRENCE;

EID: 84938252275     PISSN: None     EISSN: 17568722     Source Type: Journal    
DOI: 10.1186/s13045-015-0189-2     Document Type: Article

References (58)

1. Lichtenegger FS, Schnorfeil FM, Hiddemann W, Subklewe M. Current strategies in immunotherapy for acute myeloid leukemia. Immunotherapy. 2013;5(1):63-78.
2. Lichtenegger FS, Krupka C, Köhnke T, Subklewe M. Immunotherapy for acute myeloid leukemia. Semin Hematol. 2015;52(3):207-14.
3. Aigner M, Feulner J, Schaffer S, Kischel R, Kufer P, Schneider K, et al. T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct. Leukemia. 2012;27(5):1107-15.
4. Krupka C, Kufer P, Kischel R, Zugmaier G, Bögeholz J, Köhnke T, et al. CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood. 2014;123(3):356-65.
5. Laszlo GS, Gudgeon CJ, Harrington KH, Dell'Aringa J, Newhall KJ, Means GD, et al. Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML. Blood. 2014;123(4):554-61.
6. Arndt C, von Bonin M, Cartellieri M, Feldmann A, Koristka S, Michalk I, et al. Redirection of T cells with a first fully humanized bispecific CD33-CD3 antibody efficiently eliminates AML blasts without harming hematopoietic stem cells. Leukemia. 2013;27(4):964-7.
7. Mardiros A, Dos Santos C, McDonald T, Brown CE, Wang X, Budde LE, et al. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and anti-tumor effects against human acute myeloid leukemia. Blood. 2013;122(18):3138-48.
8. Ritchie DS, Neeson PJ, Khot A, Peinert S, Tai T, Tainton K, et al. Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther. 2013;21(11):2122-9.
9. Berger R, Rotem-Yehudar R, Slama G, Landes S, Kneller A, Leiba M, 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(10):3044-51.
10. Shi L, Chen S, Yang L, Li Y. The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol. 2013;6(1):74.
11. Andersen MH. The targeting of immunosuppressive mechanisms in hematological malignancies. Leukemia. 2014;28(9):1784-92.
12. Shimauchi T, Kabashima K, Nakashima D, Sugita K, Yamada Y, Hino R, et al. Augmented expression of programmed death-1 in both neoplastic and non-neoplastic CD4+ T-cells in adult T-cell leukemia/lymphoma. Int J Cancer. 2007;121(12):2585-90.
13. Kozako T, Yoshimitsu M, Fujiwara H, Masamoto I, Horai S, White Y, et al. PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients. Leukemia. 2009;23(2):375-82.
14. Mumprecht S, Schürch C, Schwaller J, Solenthaler M, Ochsenbein AF. Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression. Blood. 2009;114(8):1528-36.
15. Christiansson L, Söderlund S, Svensson E, Mustjoki S, Bengtsson M, Simonsson B, et al. Increased level of myeloid-derived suppressor cells, programmed death receptor ligand 1/programmed death receptor 1, and soluble CD25 in Sokal high risk chronic myeloid leukemia. PLoS One. 2013;8(1), e55818.
16. Nunes C, Wong R, Mason M, Fegan C, Man S, Pepper C. Expansion of a CD8(+)PD-1(+) replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression. Clin Cancer Res. 2012;18(3):678-87.
17. Riches JC, Davies JK, McClanahan F, Fatah R, Iqbal S, Agrawal S, et al. T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production. Blood. 2013;121(9):1612-21.
18. Gassner FJ, Zaborsky N, Neureiter D, Huemer M, Melchardt T, Egle A, et al. Chemotherapy-induced augmentation of T cells expressing inhibitory receptors is reversed by treatment with lenalidomide in chronic lymphocytic leukemia. Haematologica. 2014;99(5):67-9.
19. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;131(6):492-9.
20. Moskophidis D, Lechner F, Pircher H, Zinkernagel RM. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature. 1993;362(6422):758-61.
21. Gallimore A, Glithero A, Godkin A, Tissot AC, Plückthun A, Elliott T, et al. Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. J Exp Med. 1998;187(9):1383-93.
22. Zajac AJ, Blattman JN, Murali-Krishna K, Sourdive DJ, Suresh M, Altman JD, et al. Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med. 1998;188(12):2205-13.
23. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006;443(7109):350-4.
24. Yamamoto T, Price DA, Casazza JP, Ferrari G, Nason M, Chattopadhyay PK, et al. Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood. 2011;117(18):4805-15.
25. Peretz Y, He Z, Shi Y, Yassine-Diab B, Goulet JP, Bordi R, et al. CD160 and PD-1 co-expression on HIV-specific CD8 T cells defines a subset with advanced dysfunction. PLoS Pathog. 2012;8(8), e1002840.
26. Oxenius A, Zinkernagel RM, Hengartner H. Comparison of activation versus induction of unresponsiveness of virus-specific CD4+ and CD8+ T cells upon acute versus persistent viral infection. Immunity. 1998;9(4):449-57.
27. Brooks DG, Teyton L, Oldstone MB, McGavern DB. Intrinsic functional dysregulation of CD4 T cells occurs rapidly following persistent viral infection. J Virol. 2005;79(16):10514-27.
28. Chlewicki LK, Velikovsky CA, Balakrishnan V, Mariuzza RA, Kumar V. Molecular basis of the dual functions of 2B4 (CD244). J Immunol. 2008;180(12):8159-67.
29. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439(7077):682-7.
30. Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11(2):141-51.
31. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793-800.
32. Cai G, Anumanthan A, Brown JA, Greenfield EA, Zhu B, Freeman GJ. CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator. Nat Immunol. 2008;9(2):176-85.
33. Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10(1):29-37.
34. Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6(12):1245-52.
35. Jones RB, Ndhlovu LC, Barbour JD, Sheth PM, Jha AR, Long BR, et al. Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. J Exp Med. 2008;205(12):2763-79.
36. Fourcade J, Sun Z, Benallaoua M, Guillaume P, Luescher IF, Sander C, 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(10):2175-86.
37. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010;207(10):2187-94.
38. Zhou Q, Munger ME, Veenstra RG, Weigel BJ, Hirashima M, Munn DH, 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(17):4501-10.
39. Koch S, Larbi A, Derhovanessian E, Ozcelik D, Naumova E, Pawelec G. Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people. Immun Ageing. 2008;5:6.
40. Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114(8):1537-44.
41. Baitsch L, Baumgaertner P, Devêvre E, Raghav SK, Legat A, Barba L, et al. Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients. J Clin Invest. 2011;121(6):2350-60.
42. Van den Hove LE, Vandenberghe P, Van Gool SW, Ceuppens JL, Demuynck H, Verhoef GE, 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(2):175-84.
43. Le Dieu R, Taussig DC, Ramsay AG, Mitter R, Miraki-Moud F, Fatah R, 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(18):3909-16.
44. Lichtenegger FS, Lorenz R, Gellhaus K, Hiddemann W, Beck B, Subklewe M. Impaired NK cells and increased T regulatory cell numbers during cytotoxic maintenance therapy in AML. Leuk Res. 2014;38(8):964-9.
45. Wendelbo Ø, Nesthus I, Sjo M, Paulsen K, Ernst P, Bruserud Ø. Functional characterization of T lymphocytes derived from patients with acute myelogenous leukemia and chemotherapy-induced leukopenia. Cancer Immunol Immunother. 2004;53(8):740-7.
46. Norde WJ, Maas F, Hobo W, Korman A, Quigley M, Kester MG, et al. PD-1/PD-L1 interactions contribute to functional T-cell impairment in patients who relapse with cancer after allogeneic stem cell transplantation. Cancer Res. 2011;71(15):5111-22.
47. Flörcken A, van Lessen A, Terwey TH, Dörken B, Arnold R, Pezzutto A, et al. Anti-leukemia T cells in AML: TNF-α+ CD8+ T cells may escape detection and possibly reflect a stage of functional impairment. Hum Vaccin Immunother. 2013;9(6):1200-4.
48. Han S, Asoyan A, Rabenstein H, Nakano N, Obst R. Role of antigen persistence and dose for CD4+ T-cell exhaustion and recovery. Proc Natl Acad Sci U S A. 2010;107(47):20453-8.
49. Antoine P, Olislagers V, Huygens A, Lecomte S, Liesnard C, Donner C, et al. Functional exhaustion of CD4+ T lymphocytes during primary cytomegalovirus infection. J Immunol. 2012;189(5):2665-72.
50. Dow C, Henderson R, Sette A, Mothé BR. CD4(+) T-cell inhibitory ligands: a tool for characterizing dysfunctional CD4(+) T cells during chronic infection. Immunology. 2013;140(1):61-9.
51. Raimondi G, Shufesky WJ, Tokita D, Morelli AE, Thomson AW. Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells. J Immunol. 2006;176(5):2808-16.
52. Romero P, Zippelius A, Kurth I, Pittet MJ, Touvrey C, Iancu EM, et al. Four functionally distinct populations of human effector-memory CD8+ T lymphocytes. J Immunol. 2007;178(7):4112-9.
53. Legat A, Speiser DE, Pircher H, Zehn D, Fuertes Marraco SA. Inhibitory receptor expression depends more dominantly on differentiation and activation than "exhaustion" of human CD8 T cells. Front Immunol. 2013;4:455.
54. Brusa D, Serra S, Coscia M, Rossi D, D'Arena G, Laurenti L, et al. The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia. Haematologica. 2013;98(6):953-63.
55. Te Raa GD, Pascutti MF, García-Vallejo JJ, Reinen E, Remmerswaal EB, Ten Berge IJ, et al. CMV-specific CD8+ T cell function is not impaired in chronic lymphocytic leukemia. Blood. 2013;123(5):717-24.
56. Fredly H, Reikvam H, Gjertsen BT, Bruserud O. Disease-stabilizing treatment with all-trans retinoic acid and valproic acid in acute myeloid leukemia: serum hsp70 and hsp90 levels and serum cytokine profiles are determined by the disease, patient age, and anti-leukemic treatment. Am J Hematol. 2012;87(4):368-76.
57. Kornblau SM, McCue D, Singh N, Chen W, Estrov Z, Coombes KR. Recurrent expression signatures of cytokines and chemokines are present and are independently prognostic in acute myelogenous leukemia and myelodysplasia. Blood. 2010;116(20):4251-61.
58. Lion E, Willemen Y, Berneman ZN, Van Tendeloo VF, Smits EL. Natural killer cell immune escape in acute myeloid leukemia. Leukemia. 2012;26(9):2019-26.