免疫调节药品：急性白血病的免疫检查站代理

Title:Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia

Volume: 18 Issue: 3

Author(s): Hanna A. Knaus, Christopher G. Kanakry, Leo Luznik, Ivana Gojo.

Affiliation:

关键词: 急性淋巴细胞白血病，急性髓系白血病，共抑制受体，免疫检查点途径，免疫逃避，免疫治疗，单克隆抗体，T细胞。

摘要: Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body's own immune system to fight leukemic cells.

Cite this article as:

Hanna A. Knaus, Christopher G. Kanakry, Leo Luznik, Ivana Gojo. , Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia, Current Drug Targets 2017; 18 (3) . https://dx.doi.org/10.2174/1389450116666150518095346