ArticleThe Journal of experimental medicine2015
TLR9 ligation in pancreatic stellate cells promotes tumorigenesis.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 158 citations in OpenAlex.
- Does Oral Microbiota Have a Close Relationship with Pancreatic Cancer? A Systematic Review and Meta-Analysis.Annals of surgical oncology · 2023Pooled it
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Microbiome-pancreatic cancer crosstalk: From tumor biology to therapeutic intervention.iMetaOmics · 2026Review
- Microbiota in pancreatic cancer: Roles in tumor initiation and progression (Review).Oncology letters · 2026Review
- Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth.Cancer cell · 2026Article
- Cancer cell-intrinsic inflammasome protein ASC links innate immunity with mitochondrial metabolism in driving pancreatic cancer.Nature communications · 2026Article
- Unveiling the gut-pancreas axis: microbial influence on stemness and tumor microenvironment of PDAC.Stem cells (Dayton, Ohio) · 2026Review
- Application of group A streptococcal collagen-like protein 1-expressing Lactococcus as a novel immunotherapeutic against pancreatic ductal adenocarcinoma.Scientific reports · 2026Article
- Cell-Free DNA (cfDNA), Its Applications in Cancer Diagnosis and Monitoring, and Its Potential Role in Regulating Cancer Metabolism.Advances in experimental medicine and biology · 2026Review
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- The association between periodontal disease and pancreatic cancer: epidemiology, mechanisms, and implications for clinical management.Frontiers in cellular and infection microbiology · 2026Review
- Emerging Roles of C-C Motif Ligand 11 (CCL11) in Cancers and Liver Diseases: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Review
- PLXDC1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Stromal Cells in Early Inflammation-Related Pancreatic Carcinogenesis-Biology and Its Potential Role in Therapeutic Targeting.Cancers · 2025Review
- Dysbiosis and extraintestinal cancers.Journal of experimental & clinical cancer research : CR · 2025Review
- The Recruitment and Immune Suppression Mechanisms of Myeloid-Derived Suppressor Cells and Their Impact on Bone Metastatic Cancer.Cancer reports (Hoboken, N.J.) · 2025Review
- The role of oral microbiota in digestive system diseases: current advances and perspectives.Journal of oral microbiology · 2025Review
- TLR9: A Double-Dealing Toll-Like Receptor.ImmunoTargets and therapy · 2025Review
- Intratumoral microbiota as cancer therapeutic target.Aging medicine (Milton (N.S.W)) · 2024Review
- Causal effect of gut microbiota on pancreatic cancer: A Mendelian randomization and colocalization study.Journal of cellular and molecular medicine · 2024Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis.
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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.