免疫检查点抑制剂所致肝脏不良反应的研究进展

Research advances in adverse liver reactions caused by immune checkpoint inhibitors

免疫检查点抑制剂通过阻断T淋巴细胞负性调控信号以达到增强T淋巴细胞抗肿瘤效应的同时,也可能造成免疫耐受失衡或正常免疫亢进从而导致免疫性肝炎。本文主要通过对免疫检查点抑制剂的治疗机制,导致肝损伤的不良反应机制、危险因素以及发生率等方面进行回顾分析,并且对免疫检查点抑制剂导致肝损伤的治疗方法进行初步归纳。认为免疫检查点抑制剂在促进抗肿瘤免疫的同时,由于作用机制的非肿瘤组织靶点特异性,可能造成非同质化的免疫相关的肝损伤,治疗上以恢复免疫稳态为主。因此,免疫检查点抑制剂应用患者的管理往往需要在治疗窗、毒性和特定损伤治疗之间取得平衡,并开展多学科协作。

Immune checkpoint inhibitors can enhance the anti-tumor effect of T cells by blocking the negative regulatory signal of T cells,and meanwhile,they may also cause the imbalance of immune tolerance or normal immune hyperfunction,thus leading to immune hepatitis.This article mainly reviews the therapeutic mechanism of immune checkpoint inhibitors,their mechanism in causing the adverse reaction of liver injury,related risk factors,and incidence rate and summarizes the treatment methods for liver injury caused by immune checkpoint inhibitors.It is believed that while promoting anti-tumor immunity,immune checkpoint inhibitors may cause non-homogeneous immune-related liver injury due to the specificity of non-tumor tissue targets,and the main purpose of treatment is to restore immune homeostasis.Therefore,the management of patients using immune checkpoint inhibitors often requires a balance between treatment window,toxicity,and treatment of specific injury,as well as multidisciplinary collaboration.