摘要
目前免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)已成为应用最广的恶性肿瘤免疫疗法,主要包括外周血细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)抑制剂、程序性细胞死亡蛋白1(programmed death protein-1/ligand-1,PD-1/PD-L1)抑制剂和淋巴细胞活化基因3(lymphocyte activation gene-3,LAG-3)抑制剂。ICIs相关的心肌炎(immune checkpoint inhibitor-associated myocarditis,ICIAM)是ICIs导致的最致命的免疫相关不良反应(immune-related adverse events,irAEs)之一。ICIs联合治疗时,ICIAM的发病率多高于单药治疗。其分子机制主要包括免疫检查点作为新抗原、肿瘤同源抗原的异位识别、免疫检查点心脏保护的阻断、自身抗体和炎症因子的产生以及微生物的调节作用等。目前已有多种治疗ICIAM药物及非药物性方案。ICIAM分子机制的探索和治疗管理方案的进步仍需多学科共同努力。
Immune checkpoint inhibitors(ICIs) are regarded as the most widely used immunotherapy for malignancies, which mainly includes inhibitors of cytotoxic T lymphocyte associated antigen-4(CTLA-4), programmed death protein-1/ligand-1(PD-1/PD-L1) and lymphocyte activation gene-3(LAG-3). One of the most fatal immune-related adverse events(irAE) resulted from ICIs is immune checkpoint inhibitor-associated myocarditis(ICIAM). The incidence of ICIAM in combination therapy is much higher than that of monotherapy. The molecular mechanisms of ICIAM mainly include immune checkpoints as neoantigens, heterotopic recognition of tumor homologous antigens, blocking the cardioprotective effect of immune checkpoints, generation of autoantibodies or inflammatory cytokines and abnormal regulation of microbial. There are several pharmacological and nonpharmacological regiments for the treatment of ICIAM. Multi-disciplinary efforts are still needed to explore the molecular mechanisms of ICIAM and to improve the treatment managements.
作者
陈怡帆
程蕾蕾
葛均波
CHEN Yi-fan;CHENG Lei-lei;GE Jun-bo(Department of Cardiology,Zhongshan Hospital,Fudan University,Shanghai Institute of Cardiovascular Diseases,Shanghai200032,China;Department of Echocardiography,Zhongshan Hospital,Fudan University,Shanghai Institute of Cardiovascular Diseases,Shanghai Institute of Medical Imaging,Shanghai 200032,China)
出处
《中国临床医学》
2022年第2期260-266,共7页
Chinese Journal of Clinical Medicine
基金
国家自然科学基金(81771840)
复旦大学附属中山医院临床研究专项基金(2020ZSLC21)
复旦大学附属中山医院智慧医疗专项(2020ZHZS16)
上海市科学技术委员会基金(18411950200)
上海介入治疗工程技术研究中心基金(19DZ2250300)。
关键词
免疫检查点抑制剂
免疫检查点抑制剂相关的心肌炎
分子机制
异位识别
自身抗体
炎症因子
immune checkpoint inhibitors
immune checkpoint inhibitor-associated myocarditis
molecular mechanisms
heterotopic recognition
autoantibodies
inflammatory cytokines
