ArticleCancer discovery2019
IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma.
Article in Cancer discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 910 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
910 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,228 citations in OpenAlex.
- Metabolic regulation and immunosuppressive functions of lipid-associated macrophages in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Pooled it
- A phase Ib/II trial of XL888 (HSP90 inhibitor) and pembrolizumab in metastatic pancreatic cancer with translational immune profiling.Cancer letters · 2026Trial
- Trial
- DRP1 depletion protects NK cells from hypoxia-induced dysfunction.Redox report : communications in free radical research · 2026Article
- Research progress of pancreatic cancer based on ferroptosis-cuproptosis interaction (Review).Oncology letters · 2026Review
- Metabolic reprogramming in cancer-associated fibroblasts: orchestrating the tumor immune microenvironment and response to immune checkpoint blockade.Experimental hematology & oncology · 2026Review
- Periductal Fibroblast Density Defines Lymphocyte Exclusion via a CD44-Dependent Stromal Checkpoint in Pancreatic Cancer.Cancer immunology research · 2026Article
- ERG Orchestrates a Dedifferentiation-Senescence-Inflammation Triad in Prostate Cancer.Molecular cancer research : MCR · 2026Article
- Multi-stromal organoid co-culture modelling reveals epithelial-fibroblast heterogeneity in pancreatic cancer and pancreatitis.Nature cell biology · 2026Article
- Context-dependent efficacy of fibroblast activation protein-targeted radionuclide therapy (FAP-TRT): the dual role of CAFs.European journal of nuclear medicine and molecular imaging · 2026Article
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Integrated Multi-Omics Reveals Cellular States and Microenvironmental Remodeling in Coexisting DCIS and IDC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An integrated spatially defined roadmap of normal and cancer-associated colon fibroblasts.Molecular systems biology · 2026Article
- Dual Functions of B7-H3-MAPK Signaling Orchestrate Tumor Immunosuppression via Regulating the Plasticity of Myeloid-derived Suppressor Cells and Fibroblasts.Cancer discovery · 2026Article
- Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.Biomarker research · 2026Review
- Review
- 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
- Review
- Targeting fibroblast activation suppresses chemotherapy-induced pro-invasive remodeling of the extracellular matrix.bioRxiv : the preprint server for biology · 2026Article
- Interleukin-1α Mediates Pancreatic Fibroblast Activation, Regulates Immune Cell Recruitment and Fibrosis in Acute and Chronic Pancreatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
850 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is poorly responsive to therapies and histologically contains a paucity of neoplastic cells embedded within a dense desmoplastic stroma. Within the stroma, cancer-associated fibroblasts (CAF) secrete tropic factors and extracellular matrix components, and have been implicated in PDAC progression and chemotherapy resistance. We recently identified two distinct CAF subtypes characterized by either myofibroblastic or inflammatory phenotypes; however, the mechanisms underlying their diversity and their roles in PDAC remain unknown. Here, we use organoid and mouse models to identify TGFβ and IL1 as tumor-secreted ligands that promote CAF heterogeneity. We show that IL1 induces LIF expression and downstream JAK/STAT activation to generate inflammatory CAFs and demonstrate that TGFβ antagonizes this process by downregulating IL1R1 expression and promoting differentiation into myofibroblasts. Our results provide a mechanism through which distinct fibroblast niches are established in the PDAC microenvironment and illuminate strategies to selectively target CAFs that support tumor growth. SIGNIFICANCE: Understanding the mechanisms that determine CAF heterogeneity in PDAC is a prerequisite for the rational development of approaches that selectively target tumor-promoting CAFs. Here, we identify an IL1-induced signaling cascade that leads to JAK/STAT activation and promotes an inflammatory CAF state, suggesting multiple strategies to target these cells
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.