Change in Programmed Death-1 And Inducible Costimulator Expression in Patients with Acute Myeloid Leukemia Following Chemotherapy and Its Cytogenetic Abnormalities
AbstractBackground: Programmed death-1 (PD-1) and inducible costimulator (ICOS) are immune checkpoint receptors participating in tumor immune evasion, which counters the activation signal provided through the T-cell receptor ligation. This study aimed to investigate the relationship between the expression of PD-1 and ICOS on mononuclear cells (MNCs) isolated from the peripheral blood of acute myeloid leukemia (AML) patients and their response to induction chemotherapy. Materials and Methods: Peripheral blood samples (5cc) were collected from 56 AML patients at first diagnosis before and after the induction therapy regimen for AML. PD-1 and ICOS expression were analyzed in all patients before and after the standard induction therapy regimen. Results: The expression of PD-1 and ICOS significantly decreased (66.7 and 16.3 fold, respectively) in AML patients following chemotherapy compared to its baseline value (P=0.01 and P=0.001, respectively). The expressions of PD-1 and ICOS were significantly different between favorable and poor risk groups. Conclusions: Lower PD-1 and ICOS expressions on the surface of MNCs before induction therapy were associated with a better response to treatments. In addition, PD-1 and ICOS expression on MNCs decreased after induction therapy.
Rotchanapanya W, Hokland P, Tunsing P, Owattanapanich W. Clinical Outcomes Based on Measurable Residual Disease Status in Patients with Core-Binding Factor Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis. J Pers Med. 2020;10(4):250.
Estey EH. Acute myeloid leukemia: 2013 update on risk-stratification and management. Am J Hematol. 2013;88(4):318-27.
Yanada M, Garcia-Manero G, Borthakur G, Ravandi F, Kantarjian H, Estey E. Relapse and death during first remission in acute myeloid leukemia. Haematologica. 2008;93(4):633-4.
Dohner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015;373(12):1136-52.
Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood. 2011;117(8):2307-18.
Shah A, Andersson TM, Rachet B, Bjorkholm M, Lambert PC. Survival and cure of acute myeloid leukaemia in England, 1971-2006: a population-based study. Br J Haematol. 2013;162(4):509-16.
Austin R, Smyth MJ, Lane SW. Harnessing the immune system in acute myeloid leukaemia. Crit Rev Oncol Hematol. 2016;103:62-77.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U 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(4):562-9.
Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 2006;27(4):195-201.
Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015-29.
Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res. 2007;13(7):2151-7.
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(8):1545-52.
Berthon C, Driss V, Liu J, Kuranda K, Leleu X, Jouy N et al. In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors. Cancer Immunol Immunother. 2010;59(12):1839-49.
Barsoum IB, Smallwood CA, Siemens DR, Graham CH. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res. 2014;74(3):665-74.
O'Neill NA, Zhang T, Braileanu G, Cheng X, Hershfeld A, Sun W et al. Pilot study of delayed ICOS/ICOS-L blockade with αCD40 to modulate pathogenic alloimmunity in a primate cardiac allograft model. Transplant Direct. 2018;4(2).
Burlion A, Brunel S, Petit NY, Olive D, Marodon G. Targeting the Human T-Cell Inducible COStimulator Molecule with a Monoclonal Antibody Prevents Graft-vs-Host Disease and Preserves Graft vs Leukemia in a Xenograft Murine Model. Front Immunol. 2017;8:756.
Begna KH, Ali W, Naseema G, Elliott MA, Al-Kali A, Litzow MR et al. Mayo Clinic experience with 1123 adults with acute myeloid leukemia. Blood Cancer J. 2021;11(3):46.
de Greef GE, van Putten WL, Boogaerts M, Huijgens PC, Verdonck LF, Vellenga E et al. Criteria for defining a complete remission in acute myeloid leukaemia revisited. An analysis of patients treated in HOVON-SAKK co-operative group studies. Br J Haematol. 2005;128(2):184-91.
Schmohl JU, Nuebling T, Wild J, Kroell T, Kanz L, Salih HR et al. 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):517-27.
Pedoeem A, Azoulay-Alfaguter I, Strazza M, Silverman GJ, Mor A. Programmed death-1 pathway in cancer and autoimmunity. Clin Immunol. 2014;153(1):145-52.
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-64. doi:10.1038/nrc3239.
Miller PL, Carson TL. Mechanisms and microbial influences on CTLA-4 and PD-1-based immunotherapy in the treatment of cancer: a narrative review. Gut Pathog. 2020;12(1):43.
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New Engl J Med. 2012;366(26):2443-54.
Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134-44.
Szczepanski MJ, Szajnik M, Czystowska M, Mandapathil M, Strauss L, Welsh A et al. Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res. 2009;15(10):3325-32.
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.
Amarnath S, Mangus CW, Wang JC, Wei F, He A, Kapoor V et al. The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci Transl Med. 2011;3(111):111ra20.
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372(4):311-9.
Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122-33.
Zhang W, Bai JF, Zuo MX, Cao XX, Chen M, Zhang Y et al. PD-1 expression on the surface of peripheral blood CD4+ T cell and its association with the prognosis of patients with diffuse large B-cell lymphoma. Cancer Med. 2016;5(11):3077-84.
MacFarlane AWt, Jillab M, Plimack ER, Hudes GR, Uzzo RG, Litwin S et al. PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection. Cancer Immunol Res. 2014;2(4):320-31.
Liersch R, Muller-Tidow C, Berdel WE, Krug U. Prognostic factors for acute myeloid leukaemia in adults--biological significance and clinical use. Br J Haematol. 2014;165(1):17-38.
Muenst S, Hoeller S, Dirnhofer S, Tzankov A. Increased programmed death-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival. Hum Pathol. 2009;40(12):1715-22.
Richendollar BG, Pohlman B, Elson P, Hsi ED. Follicular programmed death 1-positive lymphocytes in the tumor microenvironment are an independent prognostic factor in follicular lymphoma. Hum Pathol. 2011;42(4):552-7.
Smeltzer JP, Jones JM, Ziesmer SC, Grote DM, Xiu B, Ristow KM et al. Pattern of CD14+ follicular dendritic cells and PD1+ T cells independently predicts time to transformation in follicular lymphoma. Clin Cancer Res. 2014;20(11):2862-72.
Yang ZZ, Grote DM, Ziesmer SC, Xiu B, Novak AJ, Ansell SM. PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer Journal. 2015;5(2):e281.
Carreras J, Lopez-Guillermo A, Roncador G, Villamor N, Colomo L, Martinez A et al. High numbers of tumor-infiltrating programmed cell death 1-positive regulatory lymphocytes are associated with improved overall survival in follicular lymphoma. J Clin Oncol. 2009;27(9):1470-6.
Adom D, Dillon SR, Yang J, Liu H, Ramadan A, Kushekhar K et al. ICOSL+ plasmacytoid dendritic cells as inducer of graft-versus-host disease, responsive to a dual ICOS/CD28 antagonist. Sci Transl Med. 2020;12(564).
Saadi MI, Yaghobi R, Karimi MH, Geramizadeh B, Ramzi M, Zakerinia M. Association of the costimulatory molecule gene polymorphisms and active cytomegalovirus infection in hematopoietic stem cell transplant patients. Mol Biol Rep. 2013;40(10):5833-42.
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(3):747-57.
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