Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland.
Virchows Arch. 2019 Apr;474(4):475-484. doi: 10.1007/s00428-018-2445-7. Epub 2018 Sep 1.
Checkpoint inhibitors targeting the PD-1/PD-L1 axis are a promising treatment option in several tumor types. PD-L1 expression detected by immunohistochemistry is the first clinically validated predictive biomarker for response to PD-1/PD-L1 inhibitors, though its predictive value varies significantly between tumor types. With the approval of pembrolizumab monotherapy for treatment-naïve, advanced non-small cell lung cancer, PD-L1 testing has to become broadly available in pathology laboratories. When PD-L1 testing started to be introduced in routine pathology practice, there were several open issues, which needed to be addressed in order to provide accurate results. This review will discuss the complex biological background of PD-L1 as predictive biomarker, summarize relevant clinical trials in NSCLC illustrating the origin of different PD-L1 expression cutoffs and scorings, and address issues important for PD-L1 testing including the analytical comparability of the different clinical trial-validated PD-L1 immunohistochemistry assays, the potential of laboratory-developed tests, and an overview of the different scoring algorithms.
针对 PD-1/PD-L1 轴的检查点抑制剂是几种肿瘤类型中很有前途的治疗选择。免疫组织化学检测到的 PD-L1 表达是对 PD-1/PD-L1 抑制剂反应的首个经临床验证的预测性生物标志物，但在不同肿瘤类型之间，其预测价值有很大差异。随着 pembrolizumab 单药治疗初治晚期非小细胞肺癌的获批，PD-L1 检测必须在病理实验室广泛应用。当 PD-L1 检测开始引入常规病理实践时，存在几个悬而未决的问题，需要解决这些问题才能提供准确的结果。本综述将讨论 PD-L1 作为预测性生物标志物的复杂生物学背景，总结非小细胞肺癌相关的临床试验，说明不同 PD-L1 表达截断值和评分的起源，并讨论 PD-L1 检测的重要问题，包括不同临床试验验证的 PD-L1 免疫组织化学检测的分析可比性、实验室开发的检测的潜力，以及不同评分算法的概述。
