PD-1/PD-L1抑制剂疗效相关生物预测标记物的研究进展

Research advances in predictive biomarkers of anti PD-1/PD-L1 immunotherapy

PD-1/PD-L1检查点抑制剂疗法在癌症治疗中取得了里程碑式的突破,但疗效差异很大。因此,能够用于疗效评价的生物学标记物的研究对于PD-1/PD-L1抗体药物的应用很重要。本文讨论了PD-1/PD-L1抗体疗效相关生物预测标记物的研究进展。PD-L1表达是对PD-1/PD-L1抗体疗效预测的逻辑生物标记,然而PD-L1表达对该药物的预测价值目前有很大争论。一些其他生物标记也陆续得到关注,如TIL、错配修复基因(MMR)、肿瘤基因突变负荷(TMB)、癌基因突变(EGFR、ALK、KRAS),需要达成共识和标准化,以便在未来的研究中广泛应用。

Despite the marked success of applications of PD-1/PD-L1 checkpoint blockades in clinical practice,the efficacy and responsiveness of these agents varies greatly among different tumor types and across individual patients.Therefore,establishment of predictive biomarkers for checkpoint blockades is of great importance to maximize the therapeutic benefits.In this review,we discuss the current progress and challenges of developing predictive biomarkers of immunotherapy responsiveness,aiming to provide directions for future studies.PD-L1 expression is a logical biomarker for the prediction of response to anti-PD-(L)1 immunotherapies.However,the predictive values of PD-L1 expressions for immunotherapy still remain controversial.Multiplex detecting methods and combined biomarkers may provide new strategies,including tumor mutation burden,some oncogene mutations,like EGFR,ALK,KRAS and STK11.As current evidence of those potential predictors,a consensus and standardization is needed to be established for popularization in future studies.