摘要
急性白血病的内在的免疫反应是通过多种机制抑制,如异常抗原表达的白血病细胞,在肿瘤微环境的免疫抑制细胞因子的分泌和抑制酶的表达,免疫细胞扩张,激活免疫检查点途径,导致T细胞功能障碍或衰竭。白血病细胞与其他肿瘤细胞相似,劫持这些抑制途径以逃避细胞毒性T淋巴细胞的免疫识别和破坏。因此,封锁免疫检查站已成为一种非常有前途的方法,以增强先天性抗肿瘤免疫,以治疗恶性肿瘤。对于这种免疫治疗策略的临床疗效的证据已经在转移性黑色素瘤患者,其中抗CTLA-4抗体和抗PD-1抗体已经彻底改变了治疗这种致命性疾病与其他治疗选择有限。为了满足急性白血病新的治疗策略的高要求,临床试验这些有前途的疗法开始。在此,我们回顾了多种抑制检查站的生物学(包括CTLA-4、PD-1、Tim-3,LAG-3,BTLA、及CD200R)和急性白血病的免疫逃避的贡献。此外,我们还讨论了急性白血病的免疫检查点抑制的临床前和临床研究的现状,即利用机体自身免疫系统对抗白血病细胞。
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。
Current Drug Targets
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.
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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
DOI https://dx.doi.org/10.2174/1389450116666150518095346 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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