Predictive potential and need for standardization of PD-L1 immunohistochemistry.

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.