Gene-expression-based T-Cell-to-Stroma Enrichment (TSE) score predicts response to immune checkpoint inhibitors in urothelial cancer

Maud Rijnders, J. Alberto Nakauma-González, Debbie G. J. Robbrecht, Alberto Gil-Jimenez, Hayri E. Balcioglu, Astrid A. M. Oostvogels, Maureen J. B. Aarts, Joost L. Boormans, Paul Hamberg, Michiel S. Heijden, Bernadett E. Szabados, Geert J. L. H. Leenders, Niven Mehra, Jens Voortman, Hans M. Westgeest, Ronald Wit, Astrid A. M. Veldt, Reno Debets () and Martijn P. Lolkema
Additional contact information
Maud Rijnders: University Medical Center Rotterdam
J. Alberto Nakauma-González: University Medical Center Rotterdam
Debbie G. J. Robbrecht: University Medical Center Rotterdam
Alberto Gil-Jimenez: The Netherlands Cancer Institute
Hayri E. Balcioglu: University Medical Center Rotterdam
Astrid A. M. Oostvogels: University Medical Center Rotterdam
Maureen J. B. Aarts: Maastricht University Medical Center
Joost L. Boormans: University Medical Center Rotterdam
Paul Hamberg: Franciscus Gasthuis & Vlietland Hospital
Michiel S. Heijden: The Netherlands Cancer Institute
Bernadett E. Szabados: Queen Mary University of London
Geert J. L. H. Leenders: University Medical Center Rotterdam
Niven Mehra: Radboud University Medical Center
Jens Voortman: Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam
Hans M. Westgeest: Amphia Hospital Breda
Ronald Wit: University Medical Center Rotterdam
Astrid A. M. Veldt: University Medical Center Rotterdam
Reno Debets: University Medical Center Rotterdam
Martijn P. Lolkema: University Medical Center Rotterdam

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Immune checkpoint inhibitors (ICI) improve overall survival in patients with metastatic urothelial cancer (mUC), but therapeutic success at the individual patient level varies significantly. Here we identify predictive markers of response, based on whole-genome DNA (n = 70) and RNA-sequencing (n = 41) of fresh metastatic biopsy samples, collected prior to treatment with pembrolizumab. We find that PD-L1 combined positivity score does not, whereas tumor mutational burden and APOBEC mutagenesis modestly predict response. In contrast, T cell-to-stroma enrichment (TSE) score, computed from gene expression signature data to capture the relative abundance of T cells and stromal cells, predicts response to immunotherapy with high accuracy. Patients with a positive and negative TSE score show progression free survival rates at 6 months of 67 and 0%, respectively. The abundance of T cells and stromal cells, as reflected by the TSE score is confirmed by immunofluorescence in tumor tissue, and its good performance in two independent ICI-treated cohorts of patients with mUC (IMvigor210) and muscle-invasive UC (ABACUS) validate the predictive power of the TSE score. In conclusion, the TSE score represents a clinically applicable metric that potentially supports the prospective selection of patients with mUC for ICI treatment.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45714-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45714-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45714-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().