ArticleCancer discovery2022
Identification of Functional Heterogeneity of Carcinoma-Associated Fibroblasts with Distinct IL6-Mediated Therapy Resistance in Pancreatic Cancer.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers.
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Who cites it
206 citing papers in PubMed.
- Metabolic reprogramming in cancer-associated fibroblasts: orchestrating the tumor immune microenvironment and response to immune checkpoint blockade.Experimental hematology & oncology · 2026Review
- 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
- A Full Spectrum Fibroblast Profiling Panel Reveals Phenotypic and Metabolic Heterogeneity of Cancer-Associated Fibroblasts at the Single-Cell Level.bioRxiv : the preprint server for biology · 2026Article
- Exercise Modulates Microbial Metabolites and Induces Stromal Remodeling in Pancreatic Cancer.Cancer research · 2026Article
- Loss of CD44 re-educates pancreatic cancer-associated fibroblasts modulating their fibrotic and immunosuppressive functions.Cell death & disease · 2026Article
- Mitophagy-Competent Cancer-Associated Fibroblasts Fuel Chemoresistance by Rewiring Pyrimidine Metabolism in Pancreatic Cancer.Cancer research · 2026Article
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Foxs1-mediated transformation of CD34EMBO molecular medicine · 2026Article
- Pancreatic Cancer-Advances in the Last 50 Years.World journal of surgery · 2026Review
- Pancreatic metastases are suppressed by photodynamic therapy and irinotecan through macrophage reprogramming in immunodeficient mice.Neoplasia (New York, N.Y.) · 2026Article
- Potential of RAD51C as a hub gene and therapeutic target in bladder cancer: insights from bioinformatics and experimental analysis.International journal of surgery (London, England) · 2026Article
- Cancer-associated fibroblast subtypes differentially modulate natural killer cells in cancer.Cell reports · 2026Article
- Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.Journal of hematology & oncology · 2026Review
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- Single-cell spatial pharmacobiology identifies conserved stromal barriers to therapeutic antibody delivery in human solid tumors.Nature biotechnology · 2026Article
- Pan-cancer single-cell atlases of mouse and human tumor-associated dendritic cells.Nature communications · 2026Article
- Review
- Local gene editing of fibroblasts in tumors reveals a new cancer-associated fibroblast state.The Journal of experimental medicine · 2026Article
146 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of fibroblasts as part of the host response to cancer. Using single-cell RNA sequencing, multiplex immunostaining, and several genetic mouse models, we identify carcinoma-associated fibroblasts (CAF) with opposing functions in PDAC progression. Depletion of fibroblast activation protein (FAP)+ CAFs results in increased survival, in contrast to depletion of alpha smooth muscle actin (αSMA)+ CAFs, which leads to decreased survival. Tumor-promoting FAP+ CAFs (TP-CAF) and tumor-restraining αSMA+ CAFs (TR-CAF) differentially regulate cancer-associated pathways and accumulation of regulatory T cells. Improved efficacy of gemcitabine is observed when IL6 is deleted from αSMA+ CAFs but not from FAP+ CAFs using dual-recombinase genetic PDAC models. Improved gemcitabine efficacy due to lack of IL6 synergizes with anti-PD-1 immunotherapy to significantly improve survival of PDAC mice. Our study identifies functional heterogeneity of CAFs in PDAC progression and their different roles in therapy response. SIGNIFICANCE: PDAC is associated with accumulation of dense stroma consisting of fibroblasts and extracellular matrix that regulate tumor progression. Here, we identify two distinct populations of fibroblasts with opposing roles in the progression and immune landscape of PDAC. Our findings demonstrate that fibroblasts are functionally diverse with therapeutic implications. This article is highlighted in the In This Issue feature, p. 1397.
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