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Biomarkers in renal cell carcinoma: Towards a more selective immune checkpoint inhibition
J Sarkis1, J Assaf2, M Alkassis1
1Department of Urology, Hotel-Dieu de France Hospital, Beirut, Lebanon.
Abstract:
Immune checkpoint inhibitors such as programmed death protein 1/programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein 4 inhibitors are already playing a central role in the treatment of metastatic renal cell carcinoma. However, they seem to be only effective in a subset of patients, with a high risk of innate and adaptive tumor resistance. Consequently, biomarkers capable of predicting immune treatment efficacy in advanced renal cancer are needed both in the clinical and the experimental setting. We hereby present a brief summary of evidence on the most studied biomarkers in metastatic renal cell carcinoma with a focus on the possible future place of T cell immunoglobulin and mucin domain-3 (TIM-3).
Insights
Biomarkers are needed to predict response to immune checkpoint inhibitors in metastatic renal cell carcinoma. This review focuses on established biomarkers and the potential role of T cell immunoglobulin and mucin domain-3 (TIM-3).
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Metastatic renal cell carcinoma (mRCC) treatment increasingly utilizes immune checkpoint inhibitors (ICIs) targeting programmed death protein 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
- ICI efficacy in mRCC is limited to a subset of patients, with significant challenges posed by innate and adaptive tumor resistance.
- The absence of reliable biomarkers hinders the prediction of treatment response and the optimization of ICI therapy in advanced renal cancer.
Purpose of the Study:
- To summarize current evidence on biomarkers for predicting ICI efficacy in metastatic renal cell carcinoma.
- To explore the potential future role of T cell immunoglobulin and mucin domain-3 (TIM-3) as a predictive biomarker in mRCC.
Main Methods:
- Review of existing scientific literature on biomarkers in metastatic renal cell carcinoma.
- Focus on established predictive biomarkers for immune checkpoint inhibitor therapy.
- Analysis of preclinical and clinical data regarding T cell immunoglobulin and mucin domain-3 (TIM-3) in renal cancer.
Main Results:
- Several biomarkers are under investigation for predicting response to PD-1/PD-L1 and CTLA-4 inhibitors in mRCC.
- Tumor resistance mechanisms contribute to the heterogeneity of ICI treatment outcomes.
- Emerging data suggests TIM-3 may represent a promising biomarker for ICI efficacy in mRCC.
Conclusions:
- Predictive biomarkers are crucial for stratifying patients and improving outcomes in mRCC treated with ICIs.
- Further research is warranted to validate TIM-3 and other novel biomarkers for clinical application in advanced renal cancer.
- Identifying predictive biomarkers will facilitate personalized treatment strategies and overcome resistance to immunotherapy in mRCC.
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