PD-L1 expression testing in non-small cell lung cancer.

Area of Science:

• Oncology
• Immunology
• Biomarker Research

Background:

• Immunotherapy, specifically immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1, has become a cornerstone in advanced non-small cell lung cancer (NSCLC) treatment.
• ICIs demonstrate superior efficacy compared to traditional chemotherapy in NSCLC patients.
• Approved ICIs include nivolumab, atezolizumab, pembrolizumab, and durvalumab, used in various treatment settings for NSCLC.

Purpose of the Study:

• To review the current role of PD-L1 expression as a predictive biomarker for ICI response in NSCLC.
• To highlight the limitations and controversies surrounding PD-L1 testing.
• To introduce emerging biomarkers as potential alternatives for guiding ICI therapy in NSCLC.

Main Methods:

• Review of current literature on immunotherapy and biomarkers in NSCLC.
• Analysis of the clinical utility and challenges of PD-L1 expression testing via immunohistochemistry (IHC).
• Exploration of novel biomarkers including tumor mutation burden, neoantigens, microbiome, and gene expression signatures.

Main Results:

• PD-L1 expression is a widely used biomarker for predicting response to PD-1/PD-L1 inhibitors in NSCLC.
• Significant variability and unresolved issues exist in PD-L1 testing methods (antibodies, platforms, cell types, thresholds, sample collection).
• Emerging biomarkers show promise for more accurate prediction of ICI response in NSCLC.

Conclusions:

• While PD-L1 expression is a valuable tool, its limitations necessitate the exploration of alternative biomarkers.
• Novel biomarkers assessing tumor mutation burden, neoantigens, and the tumor microenvironment may offer more reliable guidance for ICI selection in NSCLC.
• Continued research into advanced biomarkers is crucial for optimizing immunotherapy outcomes in NSCLC.