Diagnosis and Management of Adverse Reactions to Immune Checkpoint Inhibitors

近十年，免疫疗法的兴起为癌症病人带来了福音，特别是免疫检查点抑制剂(Immune checkpoint inhibitors, ICIs)彻底开拓了癌症治疗的新局面。免疫疗法的主要目标是使抗肿瘤细胞恢复和加强免疫识别及消除恶性肿瘤细胞的能力，其中以细胞毒性T淋巴细胞相关蛋白4 (Cytotoxic T lymphocyte associated antigen4, CTLA-4)和程序性死亡蛋白-1 (Programmed death protein1, PD-1)、程序性死亡蛋白配体-1 (Programmed death protein ligand-1, PD-L1)为代表药物。随着越来越多ICIs药物在临床获批使用，获益同时，伴随的是产生一系列的免疫相关不良事件(Immune-related adverse events, irAEs)，临床约40%的肿瘤患者使用ICIs后会出现皮疹、肺炎、结肠炎、肝炎、甲状腺炎等各种irAEs。其中皮肤、肠道、内分泌、肺部和肌肉骨骼系统的irAEs相对常见，而心血管、血液、肾脏、神经和眼部的irAEs则较为少见，因此需要临床医生高度警惕。本文对ICIs引起的相关不良反应，按系统分类进行综述，目的使临床医生对irAEs的临床表现、诊断与处理以全面了解。Over the past decade, the emergence of immunotherapy has brought new hope to cancer patients, particularly as immune checkpoint inhibitors (ICIs) have revolutionized the landscape of cancer treatment. The primary objective of immunotherapy is to restore and enhance the ability of antitumor cells to recognize and eliminate malignant cells, with cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), programmed death protein-1 (PD-1), and programmed death protein ligand-1 (PD-L1) serving as representative therapeutic targets. However, alongside the increasing clinical approval and utilization of ICIs, their benefits are accompanied by a spectrum of immune-related adverse events (irAEs). Approximately 40% of cancer patients receiving ICIs develop various irAEs, including rash, pneumonitis, colitis, hepatitis, and thyroiditis. Cutaneous, gastrointestinal, endocrine, pulmonary, and musculoskeletal irAEs are relatively common, while cardiovascular, hematologic, renal, neurological, and ocular irAEs occur less frequently, necessitating heightened clinical vigilance. This review systematically categorizes and summarizes ICI-associated adverse reactions by affected organ systems, aiming to provide clinicians with a comprehensive understanding of the clinical manifestations, diagnosis, and management of irAEs.