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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*  

Abstract:


Background: PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of a variety of solid tumors. And 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.

Main body: 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 in the field of 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 implied that PD-1/PD-L1 inhibitors could help patients fight against leukemia. However, other researchers reported the opposite results.

Conclusions: 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.

Affiliation:

Department of Pediatrics, Renmin Hospital, Wuhan University, Wuhan 430060, Hubei Medical Devices, Quality Supervision and Test Institute, Wuhan 430075, Department of Pediatrics, Renmin Hospital, Wuhan University, Wuhan 430060, Department of Pediatrics, Renmin Hospital, Wuhan University, Wuhan 430060, School of Computer Science, The University of Adelaide, Adelaide, South Australia



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