Boll, Lilian MarieVázquez Montes de Oca, SergioCamarena, Marta E.Castelo Valdueza, RobertBellmunt Molins, Joaquim, 1959-Perera Bel, JúliaAlbà Soler, Mar2025-05-082025-05-082025Boll 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/s41467-025-56462-02041-1723http://hdl.handle.net/10230/70328Advanced 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.application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-025-56462-0Bladder cancerCancerComputational biology and bioinformaticsinfo:eu-repo/semantics/openAccess