PD-L1 testing by immunohistochemistry in immuno-oncology

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• Immunotherapy using immune checkpoint inhibitors (ICIs) targeting Programmed cell death ligand 1 (PD-L1) and Programmed Death Receptor 1 (PD-1) has transformed cancer treatment.
• However, patient response to ICIs is limited, with only approximately 30% benefiting.

Purpose of the Study:

• To review the role of PD-L1 immunohistochemistry (IHC) as a predictive biomarker for immunotherapy response.
• To highlight the complexities and challenges in PD-L1 testing and propose optimization strategies.

Main Methods:

• Review of current literature on PD-L1 testing in immuno-oncology.
• Discussion of preanalytical, analytical, and clinical factors influencing PD-L1 assay performance.

Main Results:

• Tumor PD-L1 expression via IHC is a key predictive biomarker for ICI selection.
• Significant challenges exist, including the need for specific companion diagnostics and high inter-assay variability in performance and cutoff levels.

Conclusions:

• Optimizing PD-L1 assessment is crucial for improving patient selection for immunotherapy.
• Addressing preanalytical, analytical, and clinical issues in PD-L1 testing is essential for maximizing its utility as a predictive biomarker.