免疫治疗相关不良反应研究进展

Current research status on immune-related adverse events

免疫检查点抑制剂(ICI)在过去十年迅速发展,并成为最具有前景的肿瘤治疗之一。但ICI打破了机体的免疫平衡,降低了T细胞耐受性,导致机体产生一系列的免疫治疗相关不良反应(IRAE)。IRAE可以累及全身多脏器,包括内分泌、胃肠道、呼吸道和皮肤系统等,临床症状均不特异,尚无高特异性及高敏感性的预测因子出现。轻度的IRAE可以通过停药缓解,严重的IRAE需要积极治疗,一线治疗为糖皮质激素,激素效果不佳可考虑免疫抑制剂,但目前最佳免疫抑制剂选择尚存争议。本综述概述了IRAE的流行病学及可能机制,以及一些有潜力的预测性生物标志物,并介绍了几种免疫治疗相关脏器毒性及管理方法。

Immune checkpoint inhibitors have progressed rapidly over the past decade and have become one of the most promising oncology treatments.However,immune checkpoint inhibitors reduce T-cell tolerance and lead to a unique spectrum of immune-related adverse events(IRAE).IRAE can involve multiple systems,including endocrine,gastrointestinal,respiratory and skin systems and there is no predictive marker with high specificity and sensitivity.Mild IRAE can be alleviated by discontinuing immune checkpoint inhibitors while severe IRAEs require active intervention.The first-line treatment is glucocorticoids,and immunosuppressants can be considered in refractory cases.However the optimal choice of immunosuppressants is currently controversial.This review provides an overview of the epidemiology and possible mechanisms of immune-related adverse events,outlines some promising predictive biomarkers,and describes several immunotherapy-related organ toxicity and management.