ArticleCancer research2025
Dissecting FAP+ Cell Diversity in Pancreatic Cancer Uncovers an Interferon-Response Subtype of Cancer-Associated Fibroblasts with Tumor-Restraining Properties.
Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Therapeutic targeting of cancer-associated fibroblasts with oncolytic virus in preclinical models of intrahepatic cholangiocarcinoma.Molecular therapy. Oncology · 2026Article
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The FAP × CD3 bispecific antibody OMTX305 induces T cell-mediated antitumor effects in patient-derived ex vivo models of solid tumors.Science advances · 2026Article
- Article
- Loss of CD44 re-educates pancreatic cancer-associated fibroblasts modulating their fibrotic and immunosuppressive functions.Cell death & disease · 2026Article
- CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis.Nature communications · 2026Article
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Spatiotemporally Ultrasound-Controlled Nanoparticles Reprogramming Immunostimulatory Antigen-Presenting Cancer-Associated Fibroblasts to Enhance Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emergence of a mixed CAF population by FAP-CD3 T-cell engager limits therapeutic efficacy.Journal for immunotherapy of cancer · 2026Article
- A single-cell and machine learning framework identifies CAFs-associated signatures linking stromal heterogeneity to immune regulation in pancreatic cancer.Journal of gastrointestinal oncology · 2026Article
- Immune-driven stromal inflammation in pancreatic cancer within a microfluidic platform.Biofabrication · 2026Article
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- Article
- Dual roles of neutrophil extracellular traps in tumors: From pro-metastatic mechanisms to immunotherapeutic strategies (Review).Oncology letters · 2026Review
- DGAT1 Drives Racially Divergent Fibroblast Activation via ERK1/2-Dependent Tumorigenic Signaling in Prostate Cancer.Cancer research communications · 2026Article
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
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Funding
Abstract
Within the stroma of pancreatic ductal adenocarcinoma (PDAC), mesenchymal cells differentiate into cancer-associated fibroblast (CAF) subtypes that differentially mediate disease progression. Defining the regulatory mechanism and diversity of CAF subtypes could identify potential therapeutic strategies to harness the tumor-suppressive activities of CAFs. To address this, we utilized single-cell RNA sequencing to profile fibroblast activation protein-α (FAP)-expressing mesenchymal cells in human PDAC. The mesenchymal subpopulations in PDAC reflected mesenchymal cell heterogeneity found in the normal developing pancreas. In addition to characterizing inflammatory CAF and myofibroblastic CAF subpopulations in detail, the analysis uncovered a previously undescribed interferon-response CAF (ifCAF) subtype. Tumor-derived signals induced specific CAF subtypes from pancreatic stellate cells in an organoid-based coculture model, and time-course experiments revealed regulatory mechanisms that govern subtype formation. STING agonists promoted an ifCAF phenotype in vivo and in vitro. Importantly, induction of an ifCAF phenotype suppressed tumor cell invasiveness and induced an antitumor phenotype in tumor-associated neutrophils. Together, this study resolves FAP+ stromal cell heterogeneity in PDAC and identifies an ifCAF subtype that can be induced to suppress protumorigenic features of PDAC. SIGNIFICANCE: Characterization of FAP+ mesenchymal cell heterogeneity in pancreatic cancer identifies a tumor-suppressive interferon-response cancer-associated fibroblast subtype that can be induced by stimulating type I interferon signaling using STING agonists.
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