ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmunoregulation in Urological Disorders: Novel Targets and TherapiesView all 11 articles
SWI/SNF Complex Alterations Predict Immunotherapy Response in Bladder Cancer
Provisionally accepted
Jian Zhang
Yapeng WangQian YanHaitao WangQiang RanHailin ZhuWeiming LuoYangkun AoYing-ang Ji
Jing Xu
Jun Zhang
Yao Zhang
Jun Jiang*
Qiuli Liu*
Weihua Lan*- Army Medical Center of PLA, Chongqing, China
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Background Immune checkpoint inhibitors have revolutionized the treatment of urothelial bladder cancer (UBC), yet response remains limited to a subset of patients. The SWItch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex is recurrently altered across cancers, but its prevalence, functional impact, and predictive value in UBC remain unclear. This study aimed to comprehensively delineate the mutational spectrum of SWI/SNF genes in UBC and assess their utility as predictive biomarkers for response to immune checkpoint blockade. Methods We analyzed tumor specimens from 49 patients in the Daping Cohort and integrated data from five independent public cohorts comprising 2,280 cases in total. Somatic alterations were identified using targeted or whole-exome sequencing, and transcriptomic profiles were obtained from RNA sequencing datasets. Survival outcomes were evaluated using Kaplan–Meier survival analysis and time-dependent ROC curves. Tumor immune landscape was characterized via xCell-based deconvolution and corroborated by multiplex immunofluorescence on institutional samples. Prognostic modeling was performed across 65 machine-learning configurations, encompassing survival SVM, CoxBoost, and stepwise Cox, with external validation in independent cohorts. Results SWI/SNF alterations were present in 42.8% of UBCs, with the highest frequencies in ARID1A, ARID1B, ARID2, SMARCA4, and PBRM1. Tumors haboring these alterations displayed higher tumor mutational burden, increased neoantigen load, an immune-inflamed microenvironment, and a significantly improved overall survival following immune checkpoint blockade (p < 0.05). Genotype-specific models achieved strong prognostic discrimination (C-index > 0.75), with AUCs up to 0.909 in SWI/SNF-mutant and 0.772 in wild-type tumors, substantially outperforming single-modality biomarkers. Conclusions SWI/SNF alterations define an immunotherapy-responsive stratification of UBC. The accompanying genotype-specific prognostic models provide a ready-to-test framework for guiding precision immunotherapy.
Keywords: Bladder cancer, immune checkpoint inhibitors, machine-learning, Prediction model, SWI/SNF
Received: 18 Sep 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Zhang, Wang, Yan, Wang, Ran, Zhu, Luo, Ao, Ji, Xu, Zhang, Zhang, Jiang, Liu and Lan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jun Jiang
Qiuli Liu
Weihua Lan
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