The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness.
随着免疫检查点抑制剂（ICIs）的引入，癌症治疗格局发生了重大转变。接受此类治疗的患者常报告出现持久的临床和影像学缓解，但同时也存在发生免疫相关不良事件（irAEs）的潜在风险。本文回顾并讨论了ICIs的作用机制及其在调节免疫系统以增强抗肿瘤免疫应答中的关键作用。我们深入分析了由药物诱导的免疫调节导致自身耐受检查点逃逸，从而引发irAEs的复杂致病机制。同时，我们按器官类型总结了irAEs导致的主要临床表现，详细阐述了其发生率及相关风险因素。当ICIs联合使用时，irAEs的发生更为频繁；其中神经系统、心血管系统、血液系统和风湿性irAEs更常见于PD1/PD-L1抑制剂，而皮肤和胃肠道irAEs则在CTLA4抑制剂治疗中更为普遍。由于irAEs的体征和症状常缺乏特异性，其诊断（尤其是罕见类型）可能具有挑战性。鉴于其与原发性自身免疫性疾病在临床和病理生理学上的相似性，鉴别诊断有时变得复杂。总之，考虑到ICIs使用的日益广泛，这一研究领域需要更多的临床研究和实践经验，特别是开发用于预测免疫毒性的生物标志物。此外，有必要加强对临床医生和患者的教育，以提升理解和认知水平。
肿瘤(癌症)患者之家