检查点抑制剂免疫治疗相关生物标志物

Biomarkers for checkpoint inhibitor immunotherapy

目的以抗程序性死亡蛋白1为代表的免疫检查点抑制剂已改善了很多肿瘤患者的临床疗效,检查点抑制剂免疫治疗的生物预测标志物是目前的研究热点,本文对这些生物标志物的研究进展进行总结。方法应用PubMed等数据库检索系统,检索2001年7月到2020年10月的相关文献,共检索到英文文献80余篇。结果经典的检查点抑制剂免疫治疗的生物标志物包括程序性死亡蛋白1、高度微卫星不稳定或错配修复缺陷、肿瘤突变负荷、CD8;肿瘤浸润淋巴细胞,新颖但不成熟的标志物包括自然杀伤细胞、调节性T细胞、程序性死亡配体2、CXC亚族趋化因子受体3、乳腺癌组织磷脂酰肌醇-3-激酶催化亚单位α基因、肠道微生物和影像学标志物等。结论生物标志物有助于预测检查点抑制剂免疫治疗的疗效。新的预测标志物在不断出现,但不管是经典标志物还是新颖的标志物,都需要长期的临床实践研究以明确其应用效果。

Objective Immunotherapy based on immune checkpoint inhibitors,such as anti-PD-1 and anti-CTLA-4,has improved the outcome of many tumor patients.Biomarkers used to predict the efficacy of checkpoint inhibitor immunotherapy are the current research focus.This paper summarizes the research progress of these biomarkers.Methods PubMed and other database retrieval systems were used to retrieve literatures from July 2001 to October 2020.More than eighty English references were retrieved.Results The classical biomarkers of checkpoint inhibitor immunotherapy included PD-L1,MSI-H/dMMR,TMB,CD8;TILs,and the novel biomarkers included NK cells,Treg,PD-L2,CXCR3,PIK3 CA,intestinal microorganisms and radiographic markers,et al.Conclusion Biomarkers can be used to predict the efficacy of checkpoint inhibitor immunotherapy.New predictive markers have been emerging in recent years,but both classic and novel markers still require long-term clinical practice studies to confirm their application effects.