ArticleBMC cancer2025
Single-cell sequencing unveils the transcriptomic landscape of castration-resistant prostate cancer-associated fibroblasts and their association with prognosis and immunotherapy response.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Ineffectiveness of immune checkpoint inhibitors in prostate cancer: is it just a question of '-mabs'?The Journal of pathology · 2026Review
- Single-cell and spatial RNA sequencing in prostate cancer.Nature reviews. Urology · 2026Review
- Molecular Mechanisms and Immune Regulation in Prostate Cancer: A Review.International journal of molecular sciences · 2026Review
- Integrated multi-omics profiling uncovers the epigenetic, transcriptional, and metabolic landscape of prostate cancer progression.BMC cancer · 2026Article
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- The Role of Distinct Cancer-Associated Fibroblast Subtypes in Prostate Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Cellular plasticity and tumor ecosystem dynamics in prostate cancer: insights from single-cell and spatial transcriptomics.American journal of clinical and experimental urology · 2026Review
- Targeting Cancer-Associated Fibroblasts in Prostate Cancer: Recent Advances and Therapeutic Opportunities.Cancers · 2025Review
- Tumor microenvironment-mediated immune evasion and resistance in prostate cancer: mechanisms, cross-talk, and therapeutic opportunities.Clinical and experimental medicine · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
backgroundThe tumor microenvironment (TME) is increasingly acknowledged as a determinant in the malignant transformation and progression of castration-resistant prostate cancer (CRPC). Cancer-associated fibroblasts (CAFs), as a pivotal stromal cellular component in TME, are implicated in tumor progression and immune escape. However, the molecular characteristics and biological functions of CRPC-CAFs in prostate cancer necessitate further investigation.
methodsWe ascertained the differential transcriptomic profiles between CRPC-CAFs and PCa-CAFs through single-cell RNA-sequencing (scRNA-seq). Bulk RNA-seq data were employed to assess the prognostic implications of CRPC-CAFs in PCa. In addition, we examined the impact of CRPC-CAFs on the efficacy of immunotherapy and the composition of the tumor immune milieu. Furthermore, a subcutaneous PCa model was applied to determine the potential of TGF-β signaling blockade to augment the response to immunotherapeutic interventions.
resultsWe observed a pronounced increase in the proportion of CAFs in CRPC compared to those in primary PCa. The functional pathways implicated in TGF-β signaling and ECM remodeling were remarkably upregulated in CRPC-CAFs. Moreover, gene regulatory network analysis uncovered substantial differences in the transcription factor activity profiles between CRPC-CAFs and PCa-CAFs. The elevated CRPC-CAFs abundance was associated with diminished recurrence-free survival and immunotherapy insensitivity. Substantially elevated infiltration of inhibitory immune cells and upregulated expression levels of immunosuppressive molecules were observed in patients with high CRPC-CAFs abundance. Importantly, administration of anti-TGF-β therapy remarkably potentiated the efficacy of anti-PD-1 immunotherapy through upregulating the anti-tumor immune response in the PCa model.
conclusionOur results highlighted the impact of CRPC-CAFs on clinical prognosis and immunosuppressive tumor milieu, indicating that CRPC-CAFs may function as a promising therapeutic target for CRPC.
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