PD-L1 testing by immunohistochemistry in immuno-oncology

Immunotherapy, based on immune checkpoint inhibitors (ICIs) targeting the programmed cell death ligand 1 (PD-L1) and/or programmed death receptor 1 (PD-1), has substantially improved the outcomes of patients with various cancers. However, only ~30% of patients benefit from ICIs. Tumor PD-L1 expression, assessed by immunohistochemistry (IHC), is the most widely validated and used predictive biomarker to guide the selection of patients for ICIs. PD-L1 assessment may be challenging due to the necessity of different companion diagnostic assays for required specific ICIs and a relatively high level of inter-assay variability in terms of performance and cutoff levels. In this review, we discuss the role of PD-L1 IHC as a predictive test in immunotherapy (immuno-oncology), highlight the complexity of the PD-L1 testing landscape, discuss various preanalytical, analytical, and clinical issues that are associated with PD-L1 assays, and provide some insights into optimization of PD-L1 as a predictive biomarker in immuno-oncology.