Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer

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• dc.contributor.author Cañizo, Carmen G.
• dc.contributor.author Guerrero Ramos, Félix
• dc.contributor.author Pérez Escavy, Mercedes
• dc.contributor.author Lodewijk, Iris
• dc.contributor.author Suárez Cabrera, Cristian
• dc.contributor.author Morales, Lucía
• dc.contributor.author Nunes, Sandra P.
• dc.contributor.author Munera Maravilla, Ester
• dc.contributor.author Rubio, Carolina
• dc.contributor.author Sánchez, Rebeca
• dc.contributor.author Rodriguez-Izquierdo, Marta
• dc.contributor.author Martínez de Villarreal, Jaime
• dc.contributor.author Real, Francisco X.
• dc.contributor.author Castellano, Daniel
• dc.contributor.author Martín Arriscado, Cristina
• dc.contributor.author Lora Pablos, David
• dc.contributor.author Rodríguez Antolín, Alfredo
• dc.contributor.author Dueñas, Marta
• dc.contributor.author Paramio, Jesus M.
• dc.contributor.author Martínez, Víctor
• dc.date.accessioned 2025-02-05T07:09:18Z
• dc.date.available 2025-02-05T07:09:18Z
• dc.date.issued 2025
• dc.description.abstract High-risk non-muscle-invasive bladder cancer (NMIBC) presents high recurrence and progression rates. Despite the use of Bacillus Calmette-Guérin gold-standard immunotherapy and the recent irruption of anti-PD-1/PD-L1 drugs, we are missing a comprehensive understanding of the tumor microenvironment (TME) that may help us find biomarkers associated to treatment outcome. Here, we prospectively analyzed TME composition and PD-L1 expression of tumor and non-tumoral tissue biopsies from 73 NMIBC patients and used scRNA-seq, transcriptomic cohorts and tissue micro-array to validate the prognostic value of cell types of interest. Compared to non-tumoral tissue, NMIBC presented microvascular alterations, increased cancer-associated fibroblast (CAF) and myofibroblast (myoCAF) presence, and varied immune cell distribution, such as increased macrophage infiltration. Heterogeneous PD-L1 expression was observed across subsets, with macrophages showing the highest expression levels, but cancer cells as the primary potential anti-PD-L1 binding targets. Unbiased analysis revealed that myoCAF and M2-like macrophages are specifically enriched in high-grade NMIBC tumors. The topological distribution of these two cell types changed as NMIBC progresses, as shown by immunofluorescence. Only myoCAFs were associated with higher rates of progression and recurrence in three independent cohorts (888 total patients), reaching prediction values comparable to transcriptomic classes, which we further validated using tissue micro-array. Our study provides a roadmap to establish the landscape of the NMIBC TME, highlighting myoCAFs as potential prognostic markers.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cañizo CG, Guerrero-Ramos F, Perez Escavy M, Lodewijk I, Suárez-Cabrera C, Morales L, et al. Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer. Oncoimmunology. 2025 Dec;14(1):2438291. DOI: 10.1080/2162402X.2024.2438291
• dc.identifier.doi http://dx.doi.org/10.1080/2162402X.2024.2438291
• dc.identifier.issn 2162-4011
• dc.identifier.uri http://hdl.handle.net/10230/69490
• dc.language.iso eng
• dc.publisher Taylor & Francis
• dc.relation.ispartof Oncoimmunology. 2025 Dec;14(1):2438291
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2023-147517OB-100
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110758RB-I00
• dc.rights © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Bladder cancer
• dc.subject.keyword Myofibroblasts
• dc.subject.keyword PD-L1
• dc.subject.keyword Cancer-associated fibroblasts
• dc.subject.keyword Tumor microenvironment
• dc.title Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion