免疫检查点抑制剂的心脏毒性及其机制  

Cardiotoxicity and Mechanisms of Immune Checkpoint Inhibitors

作　　者：董爽[1] 胡胜[1] 欧武陵[1] 蔡茜 DONG Shuang;HU Sheng;OU Wuling;CAI Qian(The First Ward of Thoracic Oncology Department,Hubei Cancer Hospital,Wuhan 430000,China)

机构地区：[1]湖北省肿瘤医院胸部肿瘤内科一病区,武汉430079

出　　处：《肿瘤防治研究》2018年第11期858-863,共6页Cancer Research on Prevention and Treatment

摘　　要：免疫检查点抑制剂(immune checkpoint inhibitor, ICI)的发展,推动了癌症治疗的革命性变化。ICI通过细胞免疫表面检查点(immune checkpoint)蛋白刺激免疫系统识别和破坏癌细胞。然而,使用ICI还可能在靶外器官(如心脏)中诱导免疫相关的不良事件(immune-related adverse events,irAE)。心脏损害的最常见表现是心肌炎,尽管罕见,但这些脱靶效应却可能危及生命。现有数据表明,ICI通过几种机制诱导其脱靶效应,包括直接结合正常组织中表达的细胞表面蛋白、激活与脱靶组织交叉反应的T细胞、产生自身抗体或增加前炎性细胞因子的水平。更好地了解癌症免疫治疗的不利影响及其潜在机制,将有助于开发生物标志,以识别有风险的患者和预防这些irAE的方法。The development of immune checkpoint inhibitors(ICI)has revolutionized cancer treatment.ICI stimulates the immune system to recognize and destroys cancer cells via immune checkpoint proteins.However,these drugs can also induce immune-related adverse events(irAE)in off-target organs,such as the heart.The most common manifestation of heart damage is myocarditis,and these rear off-target effects can be life-threatening.Existing data indicate that ICI induces miss-target effects through several mechanisms,including direct binding to surface proteins expressed in normal tissues,activation of T cells that cross-react with miss-target tissues,production of autoantibodies and pro-inflammatory cytokines.A better understanding of the adverse effects of cancer immunotherapy and its underlying mechanisms will help to develop biomarkers to identify at-risk patients and prevent these irAEs.

关 键 词：免疫治疗 不良反应 心脏毒性 

分 类 号：R730.51[医药卫生—肿瘤]