Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Inhibitory Effect of PD-1/PD-L1 and Blockade Immunotherapy in Leukemia

Author(s): Kai Xing, Pan Zhou, Jiaojiao Li, Miao Liu* and Wei Emma Zhang*

Volume 25, Issue 9, 2022

Published on: 07 July, 2021

Page: [1399 - 1410] Pages: 12

DOI: 10.2174/1574893616666210707101516

Price: $65

Abstract

Background: PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of a variety of solid tumors. Some clinical trials have also confirmed the excellent efficacy of PD- 1/PD-L1 inhibitors on lymphoma. However, the efficacy of PD-1/PD-L1 inhibitors on leukemia remains unclear.

Introduction: To understand the connection between PD-1/PD-L1 and leukemia better, this review concentrates on the up-regulated expression of PD-1/PD-L1 and the PD-1/PD-L1 blockade trials in participants with leukemia. PD-1/PD-L1 signal performs momentously negative immunoregulation of cancer, which can inhibit the activation of cytotoxic T cells and involve in the immune escape in tumors. Activated PD-1/PD-L1 may transduce negative intracellular signals to block the mitotic cycle and the development of T-cells. Several pathways are involved in these critical biochemical processes, including MAPK, calcium, PI3K/AKT, and so on. Lately, PD-1/PD-L1 antibodies have illustrated unprecedented curative effects on Hodgkin's lymphoma and some solid tumors. Specimens from patients with leukemia demonstrated the elevated level of PD-1/PD-L1 in T lymphocytes. This finding inspired hematologists to use PD-1/PD-L1 inhibitors for subjects suffering from leukemia. Some clinical trials have implied that PD-1/PD-L1 inhibitors could help patients fight against leukemia, however, other researchers have reported the opposite results.

Conclusion: PD-1/PD-L1 is upregulated in leukemia, but the results regarding PD-1/PD-L1 blockade are mixed and more clinical trials are needed to be conducted.

Keywords: Leukemia, immune checkpoints, PD-1, PD-L1, T lymphocytes, nivolumab, pembrolizumab, clinical trials.

Next »
Graphical Abstract

[1]
Arber, D.A.; Orazi, A.; Hasserjian, R.; Thiele, J.; Borowitz, M.J.; Le Beau, M.M.; Bloomfield, C.D.; Cazzola, M.; Vardiman, J.W. The 2016 revision to the world health organization classification of myeloid neoplasms and acute leukemia. Blood, 2016, 127(20), 2391-2405.
[http://dx.doi.org/10.1182/blood-2016-03-643544] [PMID: 27069254]
[2]
Bispo, J.A.B.; Pinheiro, P.S.; Kobetz, E.K. Epidemiology and etiology of leukemia and lymphoma. Cold Spring Harb. Perspect. Med., 2020, 10(6), a034819.
[http://dx.doi.org/10.1101/cshperspect.a034819] [PMID: 31727680]
[3]
Barbui, T.; Thiele, J.; Gisslinger, H.; Kvasnicka, H.M.; Vannucchi, A.M.; Guglielmelli, P.; Orazi, A.; Tefferi, A. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: Document summary and in-depth discussion. Blood Cancer J., 2018, 8(2), 15.
[http://dx.doi.org/10.1038/s41408-018-0054-y] [PMID: 29426921]
[4]
Tallman, M.S.; Wang, E.S.; Altman, J.K.; Appelbaum, F.R.; Bhatt, V.R.; Bixby, D.; Coutre, S.E.; De Lima, M.; Fathi, A.T.; Fiorella, M.; Foran, J.M.; Hall, A.C.; Jacoby, M.; Lancet, J.; LeBlanc, T.W.; Mannis, G.; Marcucci, G.; Martin, M.G.; Mims, A.; O’Donnell, M.R.; Olin, R.; Peker, D.; Perl, A.; Pollyea, D.A.; Pratz, K.; Prebet, T.; Ravandi, F.; Shami, P.J.; Stone, R.M.; Strickland, S.A.; Wieduwilt, M.; Gregory, K.M.; Hammond, L.; Ogba, N. Acute myeloid leukemia, version 3.2019, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2019, 17(6), 721-749.
[http://dx.doi.org/10.6004/jnccn.2019.0028] [PMID: 31200351]
[5]
DeAngelo, D.J. Tailored approaches to induction therapy for acute promyelocytic leukemia. J. Clin. Oncol., 2017, 35(6), 583-586.
[http://dx.doi.org/10.1200/JCO.2016.68.4761] [PMID: 28095152]
[6]
Brown, P.A.; Wieduwilt, M.; Logan, A.; DeAngelo, D.J.; Wang, E.S.; Fathi, A.; Cassaday, R.D.; Litzow, M.; Advani, A.; Aoun, P.; Bhatnagar, B.; Boyer, M.W.; Bryan, T.; Burke, P.W.; Coccia, P.F.; Coutre, S.E.; Jain, N.; Kirby, S.; Liu, A.; Massaro, S.; Mattison, R.J.; Oluwole, O.; Papadantonakis, N.; Park, J.; Rubnitz, J.E.; Uy, G.L.; Gregory, K.M.; Ogba, N.; Shah, B. Guidelines insights: Acute lymphoblastic leukemia, version 1.2019. J. Natl. Compr. Canc. Netw., 2019, 17(5), 414-423.
[http://dx.doi.org/10.6004/jnccn.2019.0024] [PMID: 31085755]
[7]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin., 2020, 70(1), 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[8]
Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin., 2016, 66(2), 115-132.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[9]
Hoppe, R.T.; Advani, R.H.; Ai, W.Z.; Ambinder, R.F.; Armand, P.; Bello, C.M.; Benitez, C.M.; Bierman, P.J.; Boughan, K.M.; Dabaja, B.; Gordon, L.I.; Hernandez-Ilizaliturri, F.J.; Herrera, A.F.; Hochberg, E.P.; Huang, J.; Johnston, P.B.; Kaminski, M.S.; Kenkre, V.P.; Khan, N.; Lynch, R.C.; Maddocks, K.; McConathy, J.; McKinney, M.; Metzger, M.; Morgan, D.; Mulroney, C.; Rabinovitch, R.; Rosenspire, K.C.; Seropian, S.; Tao, R.; Winter, J.N.; Yahalom, J.; Burns, J.L.; Ogba, N. Hodgkin lymphoma, version 2.2020, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2020, 18(6), 755-781.
[http://dx.doi.org/10.6004/jnccn.2020.0026] [PMID: 32502987]
[10]
Mehta-Shah, N.; Horwitz, S.M.; Ansell, S.; Ai, W.Z.; Barnes, J.; Barta, S.K.; Clemens, M.W.; Dogan, A.; Fisher, K.; Goodman, A.M.; Goyal, G.; Guitart, J.; Halwani, A.; Haverkos, B.M.; Hoppe, R.T.; Jacobsen, E.; Jagadeesh, D.; Lunning, M.A.; Mehta, A.; Olsen, E.A.; Pro, B.; Rajguru, S.A.; Shanbhag, S.; Shaver, A.; Shustov, A.; Sokol, L.; Torka, P.; Torres-Cabala, C.; Wilcox, R.; William, B.M.; Zain, J.; Dwyer, M.A.; Sundar, H.; Kim, Y.H. NCCN guidelines insights: Primary cutaneous lymphomas, version 2.2020. J. Natl. Compr. Canc. Netw., 2020, 18(5), 522-536.
[http://dx.doi.org/10.6004/jnccn.2020.0022] [PMID: 32380458]
[11]
Harker-Murray, P.D.; Pommert, L.; Barth, M.J. Novel therapies potentially available for pediatric B-Cell Non-Hodgkin lymphoma. J. Natl. Compr. Canc. Netw., 2020, 18(8), 1125-1134.
[http://dx.doi.org/10.6004/jnccn.2020.7608] [PMID: 32755987]
[12]
Ishida, Y.; Agata, Y.; Shibahara, K.; Honjo, T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J., 1992, 11(11), 3887-3895.
[http://dx.doi.org/10.1002/j.1460-2075.1992.tb05481.x] [PMID: 1396582]
[13]
Nishimura, H.; Minato, N.; Nakano, T.; Honjo, T. Immunological studies on PD-1 deficient mice: Implication of PD-1 as a negative regulator for B cell responses. Int. Immunol., 1998, 10(10), 1563-1572.
[http://dx.doi.org/10.1093/intimm/10.10.1563] [PMID: 9796923]
[14]
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), 141-151.
[http://dx.doi.org/10.1016/S1074-7613(00)80089-8] [PMID: 10485649]
[15]
(a) Tseng, S.Y.; Otsuji, M.; Gorski, K.; Huang, X.; Slansky, J.E.; Pai, S.I.; Shalabi, A.; Shin, T.; Pardoll, D.M.; Tsuchiya, H. B7- DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J. Exp. Med., 2001, 193(7), 839-846.
[http://dx.doi.org/10.1084/jem.193.7.839] [PMID: 11283156]
(b) Dong, H.; Zhu, G.; Tamada, K.; Chen, L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med., 1999, 5(12), 1365-1369.
[http://dx.doi.org/10.1038/70932] [PMID: 10581077]
[16]
Wang, X.; Wang, G.; Wang, Z.; Liu, B.; Han, N.; Li, J.; Lu, C.; Liu, X.; Zhang, Q.; Yang, Q.; Wang, G. PD-1-expressing B cells suppress CD4+ and CD8+ T cells via PD-1/PD-L1-dependent pathway. Mol. Immunol., 2019, 109, 20-26.
[http://dx.doi.org/10.1016/j.molimm.2019.02.009] [PMID: 30851633]
[17]
Sun, C.; Mezzadra, R.; Schumacher, T.N. Regulation and function of the PD-L1 checkpoint. Immunity, 2018, 48(3), 434-452.
[http://dx.doi.org/10.1016/j.immuni.2018.03.014] [PMID: 29562194]
[18]
Keir, M.E.; Butte, M.J.; Freeman, G.J.; Sharpe, A.H. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol., 2008, 26, 677-704.
[http://dx.doi.org/10.1146/annurev.immunol.26.021607.090331] [PMID: 18173375]
[19]
Chemnitz, J.M.; Parry, R.V.; Nichols, K.E.; June, C.H.; Riley, J.L. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J. Immunol., 2004, 173(2), 945-954.
[http://dx.doi.org/10.4049/jimmunol.173.2.945] [PMID: 15240681]
[20]
Shi, J.; Hou, S.; Fang, Q.; Liu, X.; Liu, X.; Qi, H. PD-1 controls follicular t helper cell positioning and function. Immunity, 2018, 49(2), 264-274.e4.
[http://dx.doi.org/10.1016/j.immuni.2018.06.012] [PMID: 30076099]
[21]
Niogret, C.; Miah, S.M.S.; Rota, G.; Fonta, N.P.; Wang, H.; Held, W.; Birchmeier, W.; Sexl, V.; Yang, W.; Vivier, E.; Ho, P.C.; Brossay, L.; Guarda, G. Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells. Nat. Commun., 2019, 10(1), 1444.
[http://dx.doi.org/10.1038/s41467-019-09431-3] [PMID: 30926899]
[22]
Niogret, C.; Birchmeier, W.; Guarda, G. SHP-2 in lymphocytes’ cytokine and inhibitory receptor signaling. Front. Immunol., 2019, 10, 2468.
[http://dx.doi.org/10.3389/fimmu.2019.02468] [PMID: 31708921]
[23]
Wu, X.; Gu, Z.; Chen, Y.; Chen, B.; Chen, W.; Weng, L.; Liu, X. Application of PD-1 blockade in cancer immunotherapy. Comput. Struct. Biotechnol. J., 2019, 17, 661-674.
[http://dx.doi.org/10.1016/j.csbj.2019.03.006] [PMID: 31205619]
[24]
Lo, W.L.; Shah, N.H.; Ahsan, N.; Horkova, V.; Stepanek, O.; Salomon, A.R.; Kuriyan, J.; Weiss, A. Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT. Nat. Immunol., 2018, 19(7), 733-741.
[http://dx.doi.org/10.1038/s41590-018-0131-1] [PMID: 29915297]
[25]
Hogan, P.G. Calcium-NFAT transcriptional signalling in T cell activation and T cell exhaustion. Cell Calcium, 2017, 63, 66-69.
[http://dx.doi.org/10.1016/j.ceca.2017.01.014] [PMID: 28153342]
[26]
Baig, M.S.; Liu, D.; Muthu, K.; Roy, A.; Saqib, U.; Naim, A.; Faisal, S.M.; Srivastava, M.; Saluja, R. Heterotrimeric complex of p38 MAPK, PKCδ and TIRAP is required for AP1 mediated inflammatory response. Int. Immunopharmacol., 2017, 48, 211-218.
[http://dx.doi.org/10.1016/j.intimp.2017.04.028] [PMID: 28528205]
[27]
Nakatsuka, T.; Tateishi, K.; Kudo, Y.; Yamamoto, K.; Nakagawa, H.; Fujiwara, H.; Takahashi, R.; Miyabayashi, K.; Asaoka, Y.; Tanaka, Y.; Ijichi, H.; Hirata, Y.; Otsuka, M.; Kato, M.; Sakai, J.; Tachibana, M.; Aburatani, H.; Shinkai, Y.; Koike, K. Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation. Oncogene, 2017, 36(45), 6262-6271.
[http://dx.doi.org/10.1038/onc.2017.222] [PMID: 28692045]
[28]
Titanji, K.; Velu, V.; Chennareddi, L.; Vijay-Kumar, M.; Gewirtz, A.T.; Freeman, G.J.; Amara, R.R. Acute depletion of activated memory B cells involves the PD-1 pathway in rapidly progressing SIV-infected macaques. J. Clin. Invest., 2010, 120(11), 3878-3890.
[http://dx.doi.org/10.1172/JCI43271] [PMID: 20972331]
[29]
Salimzadeh, L.; Le Bert, N.; Dutertre, C.A.; Gill, U.S.; Newell, E.W.; Frey, C.; Hung, M.; Novikov, N.; Fletcher, S.; Kennedy, P.T.; Bertoletti, A. PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection. J. Clin. Invest., 2018, 128(10), 4573-4587.
[http://dx.doi.org/10.1172/JCI121957] [PMID: 30084841]
[30]
Said, S.S.; Barut, G.T.; Mansur, N.; Korkmaz, A.; Sayi-Yazgan, A. Bacterially activated B-cells drive T cell differentiation towards Tr1 through PD-1/PD-L1 expression. Mol. Immunol., 2018, 96, 48-60.
[http://dx.doi.org/10.1016/j.molimm.2018.02.010] [PMID: 29494848]
[31]
Wu, H.; Xia, L.; Jia, D.; Zou, H.; Jin, G.; Qian, W.; Xu, H.; Li, T. PD-L1+ regulatory B cells act as a T cell suppressor in a PD-L1-dependent manner in melanoma patients with bone metastasis. Mol. Immunol., 2020, 119, 83-91.
[http://dx.doi.org/10.1016/j.molimm.2020.01.008] [PMID: 32001420]
[32]
Hsu, J.; Hodgins, J.J.; Marathe, M.; Nicolai, C.J.; Bourgeois-Daigneault, M.C.; Trevino, T.N.; Azimi, C.S.; Scheer, A.K.; Randolph, H.E.; Thompson, T.W.; Zhang, L.; Iannello, A.; Mathur, N.; Jardine, K.E.; Kirn, G.A.; Bell, J.C.; McBurney, M.W.; Raulet, D.H.; Ardolino, M. Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. J. Clin. Invest., 2018, 128(10), 4654-4668.
[http://dx.doi.org/10.1172/JCI99317] [PMID: 30198904]
[33]
Dong, W.; Wu, X.; Ma, S.; Wang, Y.; Nalin, A.P.; Zhu, Z.; Zhang, J.; Benson, D.M.; He, K.; Caligiuri, M.A.; Yu, J. The mechanism of Anti-PD-L1 antibody efficacy against PD-L1-Negative tumors identifies NK cells expressing PD-L1 as a cytolytic effector. Cancer Discov., 2019, 9(10), 1422-1437.
[http://dx.doi.org/10.1158/2159-8290.CD-18-1259] [PMID: 31340937]
[34]
Gordon, S.R.; Maute, R.L.; Dulken, B.W.; Hutter, G.; George, B.M.; McCracken, M.N.; Gupta, R.; Tsai, J.M.; Sinha, R.; Corey, D.; Ring, A.M.; Connolly, A.J.; Weissman, I.L. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature, 2017, 545(7655), 495-499.
[http://dx.doi.org/10.1038/nature22396] [PMID: 28514441]
[35]
Hartley, G.P.; Chow, L.; Ammons, D.T.; Wheat, W.H.; Dow, S.W. Programmed cell death ligand 1 (PD-L1) signaling regulates macrophage proliferation and activation. Cancer Immunol. Res., 2018, 6(10), 1260-1273.
[http://dx.doi.org/10.1158/2326-6066.CIR-17-0537] [PMID: 30012633]
[36]
Yao, S.; Wang, S.; Zhu, Y.; Luo, L.; Zhu, G.; Flies, S.; Xu, H.; Ruff, W.; Broadwater, M.; Choi, I.H.; Tamada, K.; Chen, L. PD-1 on dendritic cells impedes innate immunity against bacterial infection. Blood, 2009, 113(23), 5811-5818.
[http://dx.doi.org/10.1182/blood-2009-02-203141] [PMID: 19339692]
[37]
Park, S.J.; Namkoong, H.; Doh, J.; Choi, J.C.; Yang, B.G.; Park, Y.; Chul Sung, Y. Negative role of inducible PD-1 on survival of activated dendritic cells. J. Leukoc. Biol., 2014, 95(4), 621-629.
[http://dx.doi.org/10.1189/jlb.0813443] [PMID: 24319287]
[38]
Lim, T.S.; Chew, V.; Sieow, J.L.; Goh, S.; Yeong, J.P.; Soon, A.L.; Ricciardi-Castagnoli, P. PD-1 expression on dendritic cells suppresses CD8+ T cell function and antitumor immunity. OncoImmunology, 2015, 5(3), e1085146.
[http://dx.doi.org/10.1080/2162402X.2015.1085146] [PMID: 27141339]
[39]
Unger, W.W.; Laban, S.; Kleijwegt, F.S.; van der Slik, A.R.; Roep, B.O. Induction of Treg by monocyte-derived DC modulated by vitamin D3 or dexamethasone: Differential role for PD-L1. Eur. J. Immunol., 2009, 39(11), 3147-3159.
[http://dx.doi.org/10.1002/eji.200839103] [PMID: 19688742]
[40]
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]
[41]
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.
[http://dx.doi.org/10.1016/j.clim.2017.08.021] [PMID: 28893624]
[42]
Daver, N.; Basu, S.; Garcia-Manero, G.; Cortes, J.E.; Ravandi, F.; Ning, J.; Xiao, L.; Juliana, L.; Kornblau, S.M.; Konopleva, M.; Andreeff, M.; Flores, W.; Bueso-Ramos, C.E.; Somani, N.; Blando, J.; Allison, J.; Kantarjian, H.M.; Sharma, P. Defining the immune checkpoint landscape in patients (pts) with acute myeloid leukemia (AML). Blood, 2016, 128(22), 2900.
[http://dx.doi.org/10.1182/blood.V128.22.2900.2900]
[43]
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, 5(7), e330.
[http://dx.doi.org/10.1038/bcj.2015.58] [PMID: 26230954]
[44]
Jia, B.; Wang, L.; Claxton, D.F.; Ehmann, W.C.; Rybka, W.B.; Mineishi, S.; Rizvi, S.; Shike, H.; Bayerl, M.; Schell, T.D.; Hohl, R.J.; Zheng, H. Bone marrow CD8 T cells express high frequency of PD-1 and exhibit reduced anti-leukemia response in newly diagnosed AML patients. Blood Cancer J., 2018, 8(3), 34.
[http://dx.doi.org/10.1038/s41408-018-0069-4] [PMID: 29563517]
[45]
Tan, J.; Yu, Z.; Huang, J.; Chen, Y.; Huang, S.; Yao, D.; Xu, L.; Lu, Y.; Chen, S.; Li, Y. Increased PD-1+Tim-3+ exhausted T cells in bone marrow may influence the clinical outcome of patients with AML. Biomark. Res., 2020, 8, 6.
[http://dx.doi.org/10.1186/s40364-020-0185-8] [PMID: 32082573]
[46]
Meleveedu, K.S.; Chen, D.; Nadiminti, K.; Sidiqi, H.; Khan, S.; Alkhateeb, H.; Shah, M.V.; Patnaik, M.; Hogan, W.J.; Begna, K.; Litzow, M. PD-1/PD-L1 expression in extramedullary lesions of acute myeloid leukemia. Leuk. Lymphoma, 2019, 1-4.
[http://dx.doi.org/10.1080/10428194.2019.1675880] [PMID: 31608729]
[47]
Huang, J.; Tan, J.; Chen, Y.; Huang, S.; Xu, L.; Zhang, Y.; Lu, Y.; Yu, Z.; Chen, S.; Li, Y. A skewed distribution and increased PD-1+Vβ+CD4+/CD8+ T cells in patients with acute myeloid leukemia. J. Leukoc. Biol., 2019, 106(3), 725-732.
[http://dx.doi.org/10.1002/JLB.MA0119-021R] [PMID: 31136687]
[48]
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]
[49]
Lee, M.Y.; Park, C.J.; Cho, Y.U.; You, E.; Jang, S.; Seol, C.A.; Seo, E.J.; Choi, E.J.; Lee, J.H. Differences in PD-1 expression on CD8+ T-cells in chronic myeloid leukemia patients according to disease phase and TKI medication. Cancer Immunol. Immunother., 2020, 69(11), 2223-2232.
[http://dx.doi.org/10.1007/s00262-020-02617-5] [PMID: 32474769]
[50]
Hughes, A.; Clarson, J.; Tang, C.; Vidovic, L.; White, D.L.; Hughes, T.P.; Yong, A.S.M. CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors. Blood, 2017, 129(9), 1166-1176.
[http://dx.doi.org/10.1182/blood-2016-10-745992] [PMID: 28049640]
[51]
Park, S.H.; You, E.; Park, C.J.; Cho, Y.U.; Jang, S.; Im, H.J.; Seo, J.J.; Park, H.S.; Lee, J.H. Increased expression of immune checkpoint programmed cell death protein-1 (PD-1) on T cell subsets of bone marrow aspirates in patients with B-Lymphoblastic leukemia, especially in relapse and at diagnosis. Cytometry B Clin. Cytom., 2020, 98(4), 336-347.
[http://dx.doi.org/10.1002/cyto.b.21879] [PMID: 32268011]
[52]
Brusa, D.; Serra, S.; Coscia, M.; Rossi, D.; Gaidano, G.; Inghirami, G.; Vaisitti, T.; Deaglio, S. The PD-1/PD-L1 axis contributes to T cell dysfunction in chronic lymphocytic leukemia. Blood, 2012, 120(21)
[http://dx.doi.org/10.1182/blood.V120.21.1778.1778]
[53]
Rusak, M.; Eljaszewicz, A. Bołkun, Ł.; Łuksza, E.; Łapuć, I.; Piszcz, J.; Singh, P.; Dąbrowska, M.; Bodzenta-Łukaszyk, A.; Kłoczko, J.; Moniuszko, M. Prognostic significance of PD-1 expression on peripheral blood CD4+ T cells in patients with newly diagnosed chronic lymphocytic leukemia. Pol. Arch. Med. Wewn., 2015, 125(7-8), 553-559.
[http://dx.doi.org/10.20452/pamw.2967] [PMID: 26140546]
[54]
Grzywnowicz, M.; Karabon, L.; Karczmarczyk, A.; Zajac, M.; Skorka, K.; Zaleska, J.; Wlasiuk, P.; Chocholska, S.; Tomczak, W.; Bojarska-Junak, A.; Dmoszynska, A.; Frydecka, I.; Giannopoulos, K. The function of a novel immunophenotype candidate molecule PD-1 in chronic lymphocytic leukemia. Leuk. Lymphoma, 2015, 56(10), 2908-2913.
[http://dx.doi.org/10.3109/10428194.2015.1017820] [PMID: 25682964]
[55]
Novák, M.; Procházka, V.; Turcsányi, P.; Papajík, T. Numbers of CD8+PD-1+ and CD4+PD-1+ cells in peripheral blood of patients with chronic lymphocytic leukemia are independent of binet stage and are significantly higher compared to healthy volunteers. Acta Haematol., 2015, 134(4), 208-214.
[http://dx.doi.org/10.1159/000381468] [PMID: 26066608]
[56]
Brodská, B. Otevřelová, P.; Šálek, C.; Fuchs, O.; Gašová, Z.; Kuželová, K. High PD-L1 expression predicts for worse outcome of leukemia patients with concomitant NPM1 and FLT3 mutations. Int. J. Mol. Sci., 2019, 20(11), E2823.
[http://dx.doi.org/10.3390/ijms20112823] [PMID: 31185600]
[57]
Huang, C.Y.; Zha, X.F.; Wen, W.R. Expression and clinical significance of pd-l1 and microrna-138-5p in patients with acute myeloid leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2019, 27(2), 373-378.
[PMID: 30998140]
[58]
Dong, Y.; Han, Y.; Huang, Y.; Jiang, S.; Huang, Z.; Chen, R.; Yu, Z.; Yu, K.; Zhang, S. PD-L1 is expressed and promotes the expansion of regulatory T cells in acute myeloid leukemia. Front. Immunol., 2020, 11, 1710.
[http://dx.doi.org/10.3389/fimmu.2020.01710] [PMID: 32849603]
[59]
Berthon, C.; Driss, V.; Liu, J.; Kuranda, K.; Leleu, X.; Jouy, N.; Hetuin, D.; Quesnel, B. 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), 1839-1849.
[http://dx.doi.org/10.1007/s00262-010-0909-y] [PMID: 20814675]
[60]
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]
[61]
Wang, C.Y.; Zhang, L.S.; Tian, F.Q.; Huang, R. Effect of PD-L1 blockade on function of dendritic cells derived from chronic myelocytic leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2008, 16(5), 1146-1149.
[PMID: 18928614]
[62]
Feucht, J.; Kayser, S.; Gorodezki, D.; Hamieh, M.; Döring, M.; Blaeschke, F.; Schlegel, P.; Bösmüller, H.; Quintanilla-Fend, L.; Ebinger, M.; Lang, P.; Handgretinger, R.; Feuchtinger, T. T-cell responses against CD19+ pediatric acute lymphoblastic leukemia mediated by bispecific T-cell engager (BiTE) are regulated contrarily by PD-L1 and CD80/CD86 on leukemic blasts. Oncotarget, 2016, 7(47), 76902-76919.
[http://dx.doi.org/10.18632/oncotarget.12357] [PMID: 27708227]
[63]
Ma, X.J.; Zhang, F.H.; Sun, L. Expression and significance of pd-l1, hsp90 and hsp90α in serum of patients with acute leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2017, 25(5), 1384-1389.
[PMID: 29070112]
[64]
Zhang, Z.F.; Zhang, Q.T.; Xin, H.Z.; Gan, S.L.; Ma, J.; Liu, Y.F.; Xie, X.S.; Sun, H. Expression of programmed death ligand-1 (pd-l1) in human acute leukemia and its clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2015, 23(4), 930-934.
[PMID: 26314420]
[65]
Brusa, D.; Serra, S.; Coscia, M.; Rossi, D.; D’Arena, G.; Laurenti, L.; Jaksic, O.; Fedele, G.; Inghirami, G.; Gaidano, G.; Malavasi, F.; Deaglio, S. The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia. Haematologica, 2013, 98(6), 953-963.
[http://dx.doi.org/10.3324/haematol.2012.077537] [PMID: 23300177]
[66]
Li, J.H.; Pang, N.N.; Zhang, Z.H.; Zhang, R.; Chen, G.; Qu, J.H. PD-1/PD-L1 expression and its implications in patients with chronic lymphocytic leukemia. Zhonghua Xue Ye Xue Za Zhi, 2017, 38(3), 198-203.
[PMID: 28395442]
[67]
Taghiloo, S.; Allahmoradi, E.; Ebadi, R.; Tehrani, M.; Hosseini-Khah, Z.; Janbabaei, G.; Shekarriz, R.; Asgarian-Omran, H. Upregulation of galectin-9 and PD-L1 immune checkpoints molecules in patients with chronic lymphocytic leukemia. Asian Pac. J. Cancer Prev., 2017, 18(8), 2269-2274.
[PMID: 28843266]
[68]
Grzywnowicz, M.; Karczmarczyk, A.; Skorka, K.; Zajac, M.; Zaleska, J.; Chocholska, S.; Tomczak, W.; Giannopoulos, K. Expression of programmed death 1 ligand in different compartments of chronic lymphocytic leukemia. Acta Haematol., 2015, 134(4), 255-262.
[http://dx.doi.org/10.1159/000430980] [PMID: 26159545]
[69]
Xu-Monette, Z.Y.; Zhou, J.; Young, K.H. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood, 2018, 131(1), 68-83.
[http://dx.doi.org/10.1182/blood-2017-07-740993] [PMID: 29118007]
[70]
Daver, N.; Garcia-Manero, G.; Basu, S.; Boddu, P.C.; Alfayez, M.; Cortes, J.E.; Konopleva, M.; Ravandi-Kashani, F.; Jabbour, E.; Kadia, T.; Nogueras-Gonzalez, G.M.; Ning, J.; Pemmaraju, N.; DiNardo, C.D.; Andreeff, M.; Pierce, S.A.; Gordon, T.; Kornblau, S.M.; Flores, W.; Alhamal, Z.; Bueso-Ramos, C.; Jorgensen, J.L.; Patel, K.P.; Blando, J.; Allison, J.P.; Sharma, P.; Kantarjian, H. Efficacy, safety, and biomarkers of response to azacitidine and nivolumab in Relapsed/Refractory acute myeloid leukemia: A nonrandomized, Open-Label, phase II study. Cancer Discov., 2019, 9(3), 370-383.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0774] [PMID: 30409776]
[71]
Ravandi, F.; Assi, R.; Daver, N.; Benton, C.B.; Kadia, T.; Thompson, P.A.; Borthakur, G.; Alvarado, Y.; Jabbour, E.J.; Konopleva, M.; Takahashi, K.; Kornblau, S.; DiNardo, C.D.; Estrov, Z.; Flores, W.; Basu, S.; Allison, J.; Sharma, P.; Pierce, S.; Pike, A.; Cortes, J.E.; Garcia-Manero, G.; Kantarjian, H.M. Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: A single-arm, phase 2 study. Lancet Haematol., 2019, 6(9), e480-e488.
[http://dx.doi.org/10.1016/S2352-3026(19)30114-0] [PMID: 31400961]
[72]
Webster, J.; Luskin, M.R.; Prince, G.T.; DeZern, A.E.; DeAngelo, D.J.; Levis, M.J.; Blackford, A.; Sharon, E.; Streicher, H.; Luznik, L.; Gojo, I. Blinatumomab in combination with immune checkpoint inhibitors of PD-1 and CTLA-4 in adult patients with Relapsed/Refractory (R/R) CD19 positive B-Cell acute lymphoblastic leukemia (ALL): Preliminary results of a phase i study. Blood, 2018, 1321.
[http://dx.doi.org/10.1182/blood-2018-99-111845]
[73]
Rauch, D.A.; Conlon, K.C.; Janakiram, M.; Brammer, J.E.; Harding, J.C.; Ye, B.H.; Zang, X.; Ren, X.; Olson, S.; Cheng, X.; Miljkovic, M.D.; Sundaramoorthi, H.; Joseph, A.; Skidmore, Z.L.; Griffith, O.; Griffith, M.; Waldmann, T.A.; Ratner, L. Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade. Blood, 2019, 134(17), 1406-1414.
[http://dx.doi.org/10.1182/blood.2019002038] [PMID: 31467059]
[74]
Cassaday, R.D.; Garcia, K.A.; Fromm, J.R.; Percival, M.M.; Turtle, C.J.; Nghiem, P.T.; Stevenson, P.A.; Estey, E.H. Phase 2 study of pembrolizumab for measurable residual disease in adults with acute lymphoblastic leukemia. Blood Adv., 2020, 4(14), 3239-3245.
[http://dx.doi.org/10.1182/bloodadvances.2020002403] [PMID: 32692850]
[75]
Ding, W.; LaPlant, B.R.; Call, T.G.; Parikh, S.A.; Leis, J.F.; He, R.; Shanafelt, T.D.; Sinha, S.; Le-Rademacher, J.; Feldman, A.L.; Habermann, T.M.; Witzig, T.E.; Wiseman, G.A.; Lin, Y.; Asmus, E.; Nowakowski, G.S.; Conte, M.J.; Bowen, D.A.; Aitken, C.N.; Van Dyke, D.L.; Greipp, P.T.; Liu, X.; Wu, X.; Zhang, H.; Secreto, C.R.; Tian, S.; Braggio, E.; Wellik, L.E.; Micallef, I.; Viswanatha, D.S.; Yan, H.; Chanan-Khan, A.A.; Kay, N.E.; Dong, H.; Ansell, S.M. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood, 2017, 129(26), 3419-3427.
[http://dx.doi.org/10.1182/blood-2017-02-765685] [PMID: 28424162]
[76]
Zheng, H.; Mineishi, S.; Claxton, D.; Zhu, J.; Zhao, C.; Jia, B.; Ehmann, W.C.; Rybka, W.B.; Naik, S.; Songdej, N.; Drabick, J.J.; Hohl, R.J. A phase I clinical trial of avelumab in combination with decitabine as first line treatment of unfit patients with AML. Am. J. Hematol., 2020, 96(2), E46-E50.
[77]
Rousselot, P.; Renard, P.; de Buyer, A.; Finet, A.; Spentchian, M.; Saiag, P. Nivolumab to control molecular response in chronic myeloid leukemia. Leuk. Res., 2018, 72, 5-6.
[http://dx.doi.org/10.1016/j.leukres.2018.07.011] [PMID: 30056299]
[78]
Albring, J.C.; Inselmann, S.; Sauer, T.; Schliemann, C.; Altvater, B.; Kailayangiri, S.; Rössig, C.; Hartmann, W.; Knorrenschild, J.R.; Sohlbach, K.; Groth, C.; Lohoff, M.; Neubauer, A.; Berdel, W.E.; Burchert, A.; Stelljes, M. PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantation. Bone Marrow Transplant., 2017, 52(2), 317-320.
[http://dx.doi.org/10.1038/bmt.2016.274] [PMID: 27892950]
[79]
Broglie, L.; Gershan, J.; Burke, M.J. Checkpoint inhibition of PD-L1 and CTLA-4 in a child with refractory acute leukemia. Int. J. Hematol. Oncol., 2019, 8(1), IJH10.
[http://dx.doi.org/10.2217/ijh-2018-0009] [PMID: 30863527]
[80]
Landego, I.; Hewitt, D.; Hibbert, I.; Dhaliwal, D.; Pieterse, W.; Grenier, D.; Wong, R.; Johnston, J.; Banerji, V. PD-1 inhibition in malignant melanoma and lack of clinical response in chronic lymphocytic leukemia in the same patients: A case series. Curr. Oncol., 2020, 27(3), 169-172.
[http://dx.doi.org/10.3747/co.27.5371] [PMID: 32669928]
[81]
Boekstegers, A.M.; Blaeschke, F.; Schmid, I.; Wiebking, V.; Immler, S.; Hoffmann, F.; Bochmann, K.; Müller, S.; Grünewald, T.G.P.; Feucht, J.; Feuchtinger, T. MRD response in a refractory paediatric T-ALL patient through anti-programmed cell death 1 (PD-1) Ab treatment associated with induction of fatal GvHD. Bone Marrow Transplant., 2017, 52(8), 1221-1224.
[http://dx.doi.org/10.1038/bmt.2017.107] [PMID: 28581460]
[82]
Schwab, K.S.; Heine, A.; Weimann, T.; Kristiansen, G.; Brossart, P. Development of hemolytic anemia in a Nivolumab-Treated patient with refractory metastatic squamous cell skin cancer and chronic lymphatic leukemia. Case Rep. Oncol., 2016, 9(2), 373-378.
[http://dx.doi.org/10.1159/000447508] [PMID: 27462240]
[83]
Kim, H.B.; Park, S.G.; Hong, R.; Kang, S.H.; Na, Y.S. Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. World J. Clin. Cases, 2020, 8(13), 2833-2840.
[http://dx.doi.org/10.12998/wjcc.v8.i13.2833] [PMID: 32742992]
[84]
(a) Okazaki, T.; Tanaka, Y.; Nishio, R.; Mitsuiye, T.; Mizoguchi, A.; Wang, J.; Ishida, M.; Hiai, H.; Matsumori, A.; Minato, N.; Honjo, T. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat. Med., 2003, 9(12), 1477-1483.
[http://dx.doi.org/10.1038/nm955] [PMID: 14595408]
(b) Nishimura, H.; Okazaki, T.; Tanaka, Y.; Nakatani, K.; Hara, M.; Matsumori, A.; Sasayama, S.; Mizoguchi, A.; Hiai, H.; Minato, N.; Honjo, T. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science, 2001, 291(5502), 319-322.
[http://dx.doi.org/10.1126/science.291.5502.319] [PMID: 11209085]

Rights & Permissions Print Cite
Article Metrics
67
1
© 2024 Bentham Science Publishers | Privacy Policy