T Cell-to-Stroma Enrichment (TSE) score: a gene expression metric that predicts response to immune checkpoint inhibitors in patients with urothelial cancer
Rijnders, M. M.; Nakauma-Gonzalez, J. A.; Robbrecht, D. G. J.; Gil-Jimenez, A.; Aarts, M. J. B.; Boormans, J. L.; Hamberg, P.; van der Heijden, M. S.; Szabados, B. E.; van Leenders, G. J. L. H.; Mehra, N.; Voortman, J.; Westgeest, H. M.; de Wit, R.; van der Veldt, A. A. M.; Debets, R.; Lolkema, M. P.
Show abstract
Immune checkpoint inhibitors (ICIs) improve overall survival in patients with metastatic urothelial cancer (mUC). To identify predictive markers of response, whole-genome DNA (n=70) and RNA-sequencing (n=41) were performed using fresh metastatic biopsies prior to treatment with pembrolizumab. PD-L1 combined positivity score did not, whereas tumor mutational burden and APOBEC mutagenesis modestly predicted response. Using gene expression analysis, we defined the T cell-to-stroma enrichment (TSE) score, a signature-based metric that captures the relative abundance of T cells and stromal cells. Patients with a positive and negative TSE score show progression-free survival rates at 6 months of 67 and 0%, respectively. The TSE score was captured by immunofluorescence in tumor tissue, and validated in two independent ICI-treated cohorts of patients with mUC (IMvigor210) and muscle-invasive UC (ABACUS). In conclusion, the TSE score represents a clinically applicable marker that potentially aids in prospectively selecting patients with mUC for ICI treatment.
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