biostudies-literatureUnknown23(1)Vranic SImmunotherapy, based on immune checkpoint inhibitors 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 immune checkpoint inhibitors. Tumor PD-L1 expression, assessed by immunohistochemistry, is the most widely validated and used predictive biomarker to guide the selection of patients for immune checkpoint inhibitors. PD-L1 assessment may be challenging due to the necessity for different companion diagnostic assays for required specific immune checkpoint inhibitors 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 immunohistochemistry 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.Biomolecules & biomedicine15-25https://www.ebi.ac.uk/biostudies/studies/S-EPMC9901897biostudies-literaturePD-L1 testing by immunohistochemistry in immuno-oncology.PMC9901897Vranic SGatalica ZfalsePD-L1 testing by immunohistochemistry in immuno-oncology.Immunotherapy, based on immune checkpoint inhibitors 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 immune checkpoint inhibitors. Tumor PD-L1 expression, assessed by immunohistochemistry, is the most widely validated and used predictive biomarker to guide the selection of patients for immune checkpoint inhibitors. PD-L1 assessment may be challenging due to the necessity for different companion diagnostic assays for required specific immune checkpoint inhibitors 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 immunohistochemistry 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.2023-01-01T00:00:00Z2023 Feb2025-04-18T16:14:44.287Z2025-04-07T03:20:08.375ZS-EPMC99018973596428710.17305/bjbms.2022.7953