免疫检查点抑制剂耐药机制及耐药后治疗策略的研究进展

摘要

免疫检查点抑制剂(Immune-checkpoint blockers,ICBs)治疗已在多种肿瘤中获得了较好的疗效,患者生活质量明显改善.然而,并不是所有接受ICBs治疗的病人在病灶控制、症状改善和生存时间等方面均获益,很多患者对首次使用ICBs治疗一段时间后出现的耐药现象,是目前临床面临的难题.本综述列举了原发性耐药和获得性耐药可能的原因.原发性耐药包括肿瘤微环境、癌细胞本身及其他相关因素;获得性耐药包括非经典的免疫共抑制分子继发性过表达、抗原提呈信号通路异常及T细胞活化杀伤功能异常等.并阐述了可能存在的多种新型联合治疗方式,包括联合放化疗及联合靶向治疗等措施.%Immune-checkpoint blockers(ICBs)have been well received in a variety of tumors,and the quality of patient life has improved significantly.However,the reasons why not all patients treated with ICBs benefit from lesion control,symptom improvement,and survival time.Many patients are resistant to the first time when they have been using ICBs for a period of time.This is a clinical challenge.This review lists possible causes of primary drug resistance and acquired resistance to ICBs.The primary resistance is associated with several mechanisms,including tumor microenvironment,cancer cells themselves and other related factors.The acquired resistance includes nonclassical immunoprecipitation molecules secondary overexpression,abnormalities of antigen presenting signal pathway and dysfunction of T cell activation killer.Finally,we have described a variety of possible new combination of treatment,including combined radiotherapy and chemotherapy,and combined targeted therapy with other measures.