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

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; PD-1; PD-L1; T lymphocytes; clinical trials; immune checkpoints; nivolumab; pembrolizumab.