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Updated: Aug 27, 2026

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Loss-of-Function Mutations in SWI/SNF Complexes Associated With Active Tumour Immune Microenvironment Clinical
Zheng Yang1, Zixuan Tian2, Renji Liang3
1Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Abstract:
Chromatin remodelling SWI/SNF complexes are recurrently altered in malignancies, and some members were found to be associated with immune checkpoint blockade (ICB) response. However, it is unclear whether SWI/SNF complex genes as a collective factor have clinical relevance. Through pan-cancer analysis of 8507 tumours across 26 types from The Cancer Genome Atlas, we demonstrate that SWI/SNF loss-of-function (LOF) mutations correlate with elevated immunogenicity markers, such as higher tumour mutational burden (TMB), neoantigen load, and microsatellite instability. SWI/SNF-LOF tumours exhibited enriched CD8+ T cell and M1-like macrophage infiltration, upregulation of major histocompatibility complex class genes, and increased expression of immunostimulators, immunoinhibitors, and chemokines. Crucially, in ICB-treated patients across discovery (n = 750) and validation (n = 562) cohorts encompassing nine cancer types, SWI/SNF-LOF status consistently predicted superior clinical outcomes, including prolonged overall survival, progression-free survival, and higher objective response rates compared to non-mutated tumours. Multivariate analysis confirmed SWI/SNF-LOF as an independent ICB response predictor independent of TMB, age, sex, or cancer type. These findings identify SWI/SNF LOF mutations as promising biomarkers of an inflamed tumour microenvironment and favourable responses to ICB across multiple solid tumours.
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