Predicting immunotherapy response of advanced bladder cancer through a meta-analysis of six independent cohorts

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  • dc.contributor.author Boll, Lilian Marie
  • dc.contributor.author Vázquez Montes de Oca, Sergio
  • dc.contributor.author Camarena, Marta E.
  • dc.contributor.author Castelo Valdueza, Robert
  • dc.contributor.author Bellmunt Molins, Joaquim, 1959-
  • dc.contributor.author Perera Bel, Júlia
  • dc.contributor.author Albà Soler, Mar
  • dc.date.accessioned 2025-05-08T06:02:12Z
  • dc.date.available 2025-05-08T06:02:12Z
  • dc.date.issued 2025
  • dc.description.abstract Advanced bladder cancer patients show very variable responses to immune checkpoint inhibitors (ICIs) and effective strategies to predict response are still lacking. Here we integrate mutation and gene expression data from 707 advanced bladder cancer patients treated with anti-PD-1/anti-PD-L1 to build highly accurate predictive models. We find that, in addition to tumor mutational burden (TMB), enrichment in the APOBEC mutational signature, and the abundance of pro-inflammatory macrophages, are major factors associated with the response. Paradoxically, patients with high immune infiltration do not show an overall better response. We show that this can be explained by the activation of immune suppressive mechanisms in a large portion of these patients. In the case of non-immune-infiltrated cancer subtypes, we uncover specific variables likely to be involved in the response. Our findings provide information for advancing precision medicine in patients with advanced bladder cancer treated with immunotherapy.
  • dc.description.sponsorship The work was supported by the following grants and agencies: 1. Research project PID2019-105595GB-I00 (R.C.) funded by MICIU/AEI/10.13039/501100011033 and PID2021-122726NB-I00 (MMA) funded by MCIN/AEI/10.13039/501100011033 and by “ERDF: A way of making Europe”, by the “European Union”; 2. Project PI22/00171 (J.B.), funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union ; 3. 2021SGR00042 by Generalitat de Catalunya (MMA); 4. Ayudas Fundación BBVA a Proyectos de Investigación Científica en Biomedicina 2021 (MMA). LMB is funded by an INPhINIT PhD fellowship from “la Caixa” Foundation (ID 100010434), under the agreement LCF/BQ/DI21/11860060.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Boll LM, Vázquez Montes de Oca S, Camarena ME, Castelo R, Bellmunt J, Perera-Bel J, et al. Predicting immunotherapy response of advanced bladder cancer through a meta-analysis of six independent cohorts. Nat Commun. 2025 Feb 20;16(1):1213. DOI: 10.1038/s41467-025-56462-0
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-025-56462-0
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/70328
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Commun. 2025 Feb 20;16(1):1213
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-105595GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-122726NB-I00
  • dc.rights © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Bladder cancer
  • dc.subject.keyword Cancer
  • dc.subject.keyword Computational biology and bioinformatics
  • dc.title Predicting immunotherapy response of advanced bladder cancer through a meta-analysis of six independent cohorts
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Departament de Medicina i Ciències de la Vida)
Articles (Hospital del Mar Research Institute)