免疫检查点抑制剂相关心肌炎分子机制研究进展

免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）已成为目前应用最广的恶性肿瘤免疫疗法，主要包括CTLA-4（cytotoxic T lymphocyte associated antigen-4）抑制剂、PD-1/PD-L1（programmed death protein-1/ligand-1）抑制剂和LAG-3（lymphocyte activation gene-3）抑制剂。ICIs导致的最致命的免疫相关不良反应（immune-related adverse events, irAE）之一为免疫检查点抑制剂相关的心肌炎（immune checkpoint inhibitor-associated myocarditis, ICIAM）。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。对于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。

Advances in molecular mechanisms of immune checkpoint inhibitor-associated myocarditis

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 non-pharmacological 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.