PD-L1作为PD-1靶向药物治疗非小细胞肺癌疗效预测生物标志的意义及其局限性

Significance and limitations of PD-L1 as a biomarker for the therapeutic effect of PD-1 targeting therapy on NSCLC patients

近两年来,以PD-1/PD-L1为主的免疫检查点抑制剂药物的研究与应用迅速兴起,PD-L1蛋白与免疫细胞受体PD-1结合可传导抑制性信号,降低T细胞的免疫功能,从而使肿瘤发生免疫逃逸。在非小细胞肺癌(NSCLC)的二线治疗方案中,这种疗法能够显著提高患者的总体生存率(OS)。目前已上市的PD-1/PD-L1抑制剂有:Nivolumab(Opdivo)、Pembrolizumab(Keytruda)、Atezolizumab(Tecentriq)。PD-L1作为目前最常用的免疫疗效预测标志物,有临床研究显示肿瘤样本中PD-L1表达越高,PD-1/PD-L1抑制剂的疗效越好。2016年10月24日,FDA批准Keytruda用于PD-L1高表达(>50%)的非小细胞肺癌患者的一线治疗。然而由于免疫组织化学染色的精确度较低及肿瘤PD-L1表达的时空异质性等原因,将PD-L1作为肺癌免疫治疗的预测生物标志物仍有争议。现本文就PD-L1作为预测生物标志物的意义及其局限性作出如下综述。

In recent two years,immune checkpoint inhibitor drugs based on PD1/PD-L1 have a rapid rise in research and clinical application,PD-L1 protein binding to immune cell receptors PD-1,which plays a role similar to the brake,can reduce the immune function of the T-cell so that the tumor immune escape.In the setting of second-line treatment of NSCLC,this therapy has obviously increased overall survival of patients in several months,PD-1/PD-L1 checkpoint inhibitors currently listed include: Nivolumab( Opdivo) 、Pembrolizumab( Keytruda) 、Atezolizumab( Tecentriq). Clinical trials targeting the PD-1/PD-L1 axis have shown that higher efficacy if expression of PD-L1 is relatively high,which PD-L1 as the most commonly used immunotherapy predictive biomarker. Pembrolizumab( Keytruda),an antibody targeting PD-1,has recently received FDA approval for the first-line treatment of patients with NSCLC whose high expression of PD-L1( >50%) in the October 24,2016. However,PD-L1 as an exclusive predictive biomarker for lung cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. This review summarizes the significance and limitations of the PD-L1 as the predictive biomarker in the NSCLC.