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Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Biomarkers that may predict response to immunotherapy in ovarian malignancies
Curtis D Chin1, Charlene M Fares2, Gottfried E Konecny2
1Department of Pathology and Laboratory Medicine.
Purpose Of Review:
Immune checkpoint blockade (ICB) is a promising area of cancer therapeutic research. Therapies targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) mechanism of tumor immune evasion have resulted in durable responses in many difficult-to-treat tumor types. While these inhibitors are being actively investigated in clinical trials for ovarian cancer, most patients fail to respond to initial treatment with immune therapy. This review focuses on biomarkers for predicting response to treatment, and discusses clinical trials using ICB for recurrent ovarian cancer.
Recent Findings:
While PD-L1 detection by immunohistochemistry (IHC) is approved as a companion or complementary diagnostic in some cancers, there are many limitations with its use as a predictive marker. Recent research has explored biomarkers beyond PD-L1 that assess for somatic mutations, immune cell infiltrate, and gene signatures.
Summary:
With improved understanding of the tumor microenvironment and genomic classifications of ovarian tumors, new diagnostics and biomarkers that supplement conventional IHC may help predict response to therapy.
Insights
Immune checkpoint blockade shows promise for ovarian cancer, but many patients do not respond. New biomarkers beyond PD-L1 are needed to predict treatment success for recurrent ovarian cancer.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Immune checkpoint blockade (ICB) targeting the PD-1/PD-L1 pathway offers durable responses in various cancers.
- Despite clinical trials for ovarian cancer, many patients exhibit primary resistance to ICB.
- Understanding tumor immune evasion mechanisms is crucial for improving treatment efficacy.
Purpose of the Study:
- To review biomarkers for predicting response to ICB in ovarian cancer.
- To discuss ongoing clinical trials of ICB for recurrent ovarian cancer.
- To explore novel biomarkers beyond PD-L1 for patient stratification.
Main Methods:
- Literature review of biomarkers and clinical trials in ovarian cancer.
- Analysis of current limitations of PD-L1 as a predictive marker.
- Exploration of emerging biomarkers including somatic mutations, immune infiltrate, and gene signatures.
Main Results:
- PD-L1 expression by IHC has limitations as a sole predictive biomarker.
- Biomarkers assessing somatic mutations, immune cell infiltration, and gene expression signatures show potential.
- Improved understanding of the tumor microenvironment aids in biomarker development.
Conclusions:
- Novel biomarkers are essential to supplement PD-L1 testing for predicting ICB response in ovarian cancer.
- Genomic classifications and tumor microenvironment insights can guide biomarker selection.
- Personalized treatment strategies incorporating advanced biomarkers may improve outcomes for ovarian cancer patients receiving ICB.
