Refining PD-1/PD-L1 assessment for biomarker-guided immunotherapy: A review
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Published on: February 5, 2020
Marek Zdrenka1, Adam Kowalewski1, Navid Ahmadi2
1Department of Tumor Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland.
Abstract:
Anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy is an increasingly crucial in cancer treatment. To date, the Federal Drug Administration (FDA) has approved four PD-L1 immunohistochemistry (IHC) staining protocols, commercially available in the form of "kits", facilitating testing for PD-L1 expression. These kits comprise four PD-L1 antibodies on two separate IHC platforms, each utilizing distinct, non-interchangeable scoring systems. Several factors, including tumor heterogeneity and the size of the tissue specimens assessed, can lead to PD-L1 status misclassification, potentially hindering the initiation of therapy. Therefore, the development of more accurate predictive biomarkers to distinguish between responders and non-responders prior to anti-PD-1/PD-L1 therapy warrants further research. Achieving this goal necessitates refining sampling criteria, enhancing current methods of PD-L1 detection, and deepening our understanding of the impact of additional biomarkers. In this article, we review potential solutions to improve the predictive accuracy of PD-L1 assessment in order to more precisely anticipate patients' responses to anti-PD-1/PD-L1 therapy, monitor disease progression and predict clinical outcomes.
Insights
Accurate prediction of anti-programmed cell death ligand 1 (anti-PD-L1) therapy response is crucial. This review explores solutions to improve PD-L1 assessment, enhancing patient stratification and treatment outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy is vital in cancer treatment.
- Four FDA-approved PD-L1 immunohistochemistry (IHC) kits exist, but use distinct, non-interchangeable scoring systems.
- Tumor heterogeneity and specimen size can cause PD-L1 status misclassification, impeding therapy initiation.
Purpose of the Study:
- To review potential solutions for improving the predictive accuracy of PD-L1 assessment.
- To identify strategies for better patient stratification for anti-PD-1/PD-L1 therapy.
- To explore methods for monitoring disease progression and predicting clinical outcomes.
Main Methods:
- Literature review of current PD-L1 detection methods and scoring systems.
- Analysis of factors contributing to PD-L1 status misclassification.
- Exploration of novel biomarkers and refined sampling criteria.
Main Results:
- Current PD-L1 IHC kits and scoring systems present challenges in consistent interpretation.
- Tumor heterogeneity and sampling bias are significant limitations in PD-L1 assessment.
- Development of more accurate predictive biomarkers is needed to optimize anti-PD-L1 therapy efficacy.
Conclusions:
- Refining sampling criteria and enhancing PD-L1 detection methods are essential.
- Integrating additional biomarkers may improve patient response prediction.
- Improved PD-L1 assessment is critical for personalized cancer immunotherapy.

