ArticleCommunications biology2025
Single-cell RNA sequencing reveals a fibroblast gene signature that promotes T-cell infiltration in muscle-invasive bladder cancer.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Single-cell transcriptomics reveals bladder microenvironment dynamics in Hunner type interstitial cystitis.iScience · 2026Article
- NOTCH3 regulates myofibroblastic CAF differentiation via the P62-ROS signaling axis to promote bladder cancer progression.Journal of experimental & clinical cancer research : CR · 2026Article
- Transcriptomic profiling across stages of non-muscle-invasive bladder cancer identifies fibroblast activation protein-alpha as a stromal biomarker associated with progression.Molecular medicine (Cambridge, Mass.) · 2026Article
- Single-cell landscape of intratumoral heterogeneity and GABA-mediated remodeling of the immune microenvironment in breast cancer metastases.Breast cancer research : BCR · 2026Article
- VSIG2 is associated with an immune-cold microenvironment and reduced response to PD-1 blockade in bladder cancer.Frontiers in cellular and infection microbiology · 2026Article
- CTHRC1Frontiers in immunology · 2026Article
- Transcriptome and single-cell RNA sequencing analysis with 101 machine learning combinations and experimental verification reveals the mechanism of action of mannose metabolism in bladder cancer.Frontiers in immunology · 2026Article
- Single-cell and spatial atlas unveil tumor-specific microenvironment convergence and a prognosis-associated PLXDC1+ myofibroblast population in metastatic bladder cancer.Journal of translational medicine · 2025Article
- Spatial ecostructural modelling of endometrial cancer identifies the key role of CD90 + CD105 + endothelial cells in tumour heterogeneity and predicts disease recurrence.Experimental hematology & oncology · 2025Article
- Nanomaterial-Enhanced Immunotherapy: Advancing T-Cell-Based Treatments for Bladder Cancer.International journal of nanomedicine · 2025Review
- Exploring of bladder cancer immune-related genes and potential therapeutic targets based on transcriptomic data and Mendelian randomization analysis.Frontiers in immunology · 2025Article
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Authors and funding
16 authors.
Funding
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Abstract
Muscle-invasive bladder cancer (MIBC) is characterized by a complex tumor microenvironment (TME) that drives aggressive progression and treatment resistance. Previous studies have highlighted the roles of cancer-associated fibroblasts (CAFs) and exhausted T (Tex) cells in MIBC, but their interactive mechanisms remain poorly understood. Here, single-cell RNA sequencing of 19 tissue samples from 12 patients-7 MIBC, 3 non-muscle-invasive bladder cancer (NMIBC), and 9 normal tissue samples-identified 13 transcriptionally distinct fibroblast clusters and 10 functionally heterogeneous T-cell subsets. Two interferon (IFN)-responsive fibroblast populations, F-ISG15 (inflammatory CAFs) and F-POSTN (myofibroblastic CAFs), were shown to predominate in the MIBC TME. In vivo experiments demonstrated that IFN-γ secreted by Tex cells polarizes CAFs to secrete CXCL12, which recruits CXCR4-expressing T cells via the CXCL12-CXCR4 chemotactic axis. Spatial analysis revealed a bidirectional loop: Tex-derived IFN-γ sustains CAF activation, whereas CAF-secreted CXCL12 amplifies Tex infiltration. Clinically, activated CAF signatures correlate with advanced disease stages and reduced patient survival in MIBC. These findings establish CXCL12 and IFN signaling as critical therapeutic targets, offering new strategies to disrupt immunosuppressive TME crosstalk and improve outcomes for MIBC patients.
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