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目的近年来,以程序性死亡受体(programmed death-1,PD-1)和细胞毒T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)抑制剂为代表的免疫检查点抑制剂在晚期黑色素瘤和肺癌等肿瘤中取得了显著疗效。开发可预测其疗效的生物标志物有助于免疫检查点抑制剂目标患者群的筛选,推动晚期恶性肿瘤个体化精准治疗的展开。本文就免疫检查点抑制剂疗效预测生物标志物进行综述,旨在为免疫检查点抑制剂的精准化临床应用提供循证医学依据。方法应用PubMed和CNKI期刊全文数据库检索系统,以“immunity checkpoint inhibitor,biomarker,prognosis”为英文关键词,以“免疫检查点抑制剂,疗效,预测”为中文关键词,检索1995-10-2017-02相关文献。纳入标准:(1)免疫检查点抑制剂的定义;(2)免疫检查点抑制剂的作用机制;(3)免疫检查点抑制剂的疗效预测因素。排除标准:(1)研究存在设计缺陷或统计方法错误,质量差;(2)数据不完整,结果不确定。根据纳入及排除标准,共检索到英文文献42篇,中文文献2篇,纳入研究进行分析。结果免疫检查点抑制剂特异性作用于人体的免疫系统,提高多种免疫细胞的抗肿瘤活性,其整体起效时间慢,但一旦起效,疗效维持时间较长。选择相应的药物疗效预测因子,在用药前筛选出免疫检查点抑制剂治疗的目标人群,对于临床抉择至关重要。PD-L1表达率、微卫星不稳定状态和肿瘤突变负荷等指标已被证明与免疫检查点抑制剂疗效相关。其他新标志物的意义有待进一步研究证实。结论 PD-L1表达率、微卫星不稳定状态和肿瘤突变负荷是目前证据较为充足的免疫检查点抑制剂疗效预测标志物。
OBJECTIVE: In recent years, immunodetection, including programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) Point inhibitors have achieved significant efficacy in tumors such as advanced melanoma and lung cancer. The development of biomarkers predicting its efficacy will facilitate the screening of target patient populations for immune checkpoint inhibitors and promote the development of accurate individualized treatment of advanced malignancies. This review summarizes the biomarkers for predicting the efficacy of immune checkpoint inhibitors in order to provide an evidence-based medical basis for the accurate clinical application of immune checkpoint inhibitors. Methods PubMed and CNKI journals full-text database retrieval system was used to search for “immunity checkpoint inhibitor, biomarker, prognosis” as the English key words and " 10-2017-02 Related Articles Inclusion criteria: (1) the definition of an immune checkpoint inhibitor; (2) the mechanism of action of the immune checkpoint inhibitor; and (3) the efficacy predictors of the immune checkpoint inhibitor. Exclusion criteria: (1) There was a design defect or poor statistical method in the study, and (2) the data was incomplete and the result was indefinite. According to inclusion and exclusion criteria, a total of 42 English articles and 2 Chinese articles were retrieved and included in the study for analysis. Results The immune checkpoint inhibitor specifically acts on the human immune system and enhances the antitumor activity of various immune cells. The overall onset time is slow, but once established, the effect maintains for a long time. Choosing the appropriate predictor of drug efficacy, screening the target population for immune checkpoint inhibitor treatment prior to treatment is crucial for clinical decision making. The indicators such as PD-L1 expression, microsatellite instability and tumor burden have been shown to be associated with the efficacy of immune checkpoint inhibitors. The significance of other new markers needs further study to confirm. Conclusion The expression of PD-L1, microsatellite instability and tumor burden are the evidence-based predictors of efficacy of immunodeficiency checkpoint inhibitor.