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Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
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Gene-expression-based T-Cell-to-Stroma Enrichment (TSE) score predicts response to immune checkpoint inhibitors in
Maud Rijnders1, J Alberto Nakauma-González1,2,3, Debbie G J Robbrecht1
1Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Nature Communications
|February 14, 2024
Summary
Predicting immunotherapy response in metastatic urothelial cancer (mUC) is crucial. The T cell-to-stroma enrichment (TSE) score accurately predicts patient response to immune checkpoint inhibitors (ICI), outperforming other markers.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immune checkpoint inhibitors (ICI) have improved survival for metastatic urothelial cancer (mUC) patients.
- However, predicting individual patient response to ICI therapy remains a significant challenge.
- Current predictive markers, like PD-L1, show variable efficacy in mUC.
Purpose of the Study:
- To identify reliable predictive biomarkers for ICI treatment response in mUC.
- To evaluate the T cell-to-stroma enrichment (TSE) score as a predictive marker for immunotherapy efficacy.
Main Methods:
- Whole-genome DNA and RNA sequencing of metastatic urothelial cancer biopsy samples from patients treated with pembrolizumab.
- Computation of the T cell-to-stroma enrichment (TSE) score using gene expression signature data.
- Validation of the TSE score in independent mUC cohorts (IMvigor210 and ABACUS) using immunofluorescence and clinical outcomes.
Main Results:
- Tumor mutational burden and APOBEC mutagenesis showed modest predictive value for ICI response.
- The TSE score demonstrated high accuracy in predicting response to immunotherapy.
- Patients with a positive TSE score had a 6-month progression-free survival rate of 67%, compared to 0% for those with a negative score.
Conclusions:
- The TSE score, reflecting T cell and stromal cell abundance, is a robust predictor of ICI response in mUC.
- The TSE score offers a clinically applicable metric for prospective patient selection for ICI therapy.
- This finding supports the use of the TSE score to optimize treatment strategies for mUC patients.
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