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Biomarkers for immune checkpoint inhibition in sarcomas - are we close to clinical implementation?
Chin Sern Yiong1,2, Tzu Ping Lin1,2, Vivian Yujing Lim1
1Translational Precision Oncology Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
Abstract:
Sarcomas are a group of diverse and complex cancers of mesenchymal origin that remains poorly understood. Recent developments in cancer immunotherapy have demonstrated a potential for better outcomes with immune checkpoint inhibition in some sarcomas compared to conventional chemotherapy. Immune checkpoint inhibitors (ICIs) are key agents in cancer immunotherapy, demonstrating improved outcomes in many tumor types. However, most patients with sarcoma do not benefit from treatment, highlighting the need for identification and development of predictive biomarkers for response to ICIs. In this review, we first discuss United States (US) Food and Drug Administration (FDA)-approved and European Medicines Agency (EMA)-approved biomarkers, as well as the limitations of their use in sarcomas. We then review eight potential predictive biomarkers and rationalize their utility in sarcomas. These include gene expression signatures (GES), circulating neutrophil-to-lymphocyte ratio (NLR), indoleamine 2,3-dioxygenase (IDO), lymphocyte activation gene 3 (LAG-3), T cell immunoglobin and mucin domain-containing protein 3 (TIM-3), TP53 mutation status, B cells, and tertiary lymphoid structures (TLS). Finally, we discuss the potential for TLS as both a predictive and prognostic biomarker for ICI response in sarcomas to be implemented in the clinic.
Insights
Identifying predictive biomarkers is crucial for improving immune checkpoint inhibitor (ICI) therapy in sarcoma patients. This review explores potential biomarkers like tertiary lymphoid structures (TLS) for better treatment response prediction.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Sarcomas are complex cancers of mesenchymal origin with limited understanding.
- Immune checkpoint inhibitors (ICIs) show promise in sarcoma treatment, but most patients do not benefit.
- There is a critical need for predictive biomarkers to guide ICI therapy in sarcoma.
Purpose of the Study:
- To review current FDA/EMA-approved biomarkers and their limitations in sarcoma.
- To explore eight potential predictive biomarkers for ICI response in sarcomas.
- To evaluate tertiary lymphoid structures (TLS) as a predictive and prognostic biomarker for ICI therapy.
Main Methods:
- Literature review of approved and potential biomarkers for ICI response.
- Analysis of gene expression signatures (GES), neutrophil-to-lymphocyte ratio (NLR), IDO, LAG-3, TIM-3, TP53 mutation status, B cells, and TLS.
- Discussion on the clinical utility and potential implementation of TLS.
Main Results:
- Current approved biomarkers have limitations in sarcoma treatment.
- Several potential biomarkers, including GES, NLR, IDO, LAG-3, TIM-3, TP53, B cells, and TLS, show promise.
- Tertiary lymphoid structures (TLS) demonstrate potential as both predictive and prognostic indicators.
Conclusions:
- Effective predictive biomarkers are essential for optimizing ICI therapy in sarcoma.
- TLS represent a promising biomarker for predicting and monitoring response to ICIs in sarcomas.
- Further research and clinical validation are needed to implement these biomarkers effectively.
