ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Increased Th17 cells in the tumor microenvironment is mediated by IL-23 via tumor-secreted prostaglandin E2.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed.
- AA in Rheumatoid Arthritis and Lupus.Reviews of physiology, biochemistry and pharmacology · 2027Review
- TGF-β-producing tBregs are associated with poor survival rates in PTGS2-high cancers.Cell death & disease · 2026Article
- Glycosylated extracellular matrix drives immune suppression by modulating macrophage-T cell crosstalk in triple-negative breast cancer.Nature communications · 2026Article
- Article
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- Calcitriol and Tacalcitol Modulate Th17 Differentiation Through Osteopontin Receptors: Age-Dependent Insights from a Mouse Breast Cancer Model.ImmunoTargets and therapy · 2025Article
- Calcitriol promotes M2 polarization of tumor-associated macrophages in 4T1 mouse mammary gland cancer via the induction of proinflammatory cytokines.Scientific reports · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Mechanistic Insights into the Roles of the IL-17/IL-17R Families in Pancreatic Cancer.International journal of molecular sciences · 2023Review
- LL-37 Might Promote Local Invasion of Melanoma by Activating Melanoma Cells and Tumor-Associated Macrophages.Cancers · 2023Article
- Vitamin D, Th17 Lymphocytes, and Breast Cancer.Cancers · 2022Review
- Cimetidine and Ibuprofen Modulate T Cell Responses in a Mouse Model of Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis.International journal of molecular sciences · 2022Article
- Identification and validation of the role of c-Myc in head and neck squamous cell carcinoma.Frontiers in oncology · 2022Article
- Molecular biochemical aspects of salt (sodium chloride) in inflammation and immune response with reference to hypertension and type 2 diabetes mellitus.Lipids in health and disease · 2021Review
- Review
- IL-12 Family Cytokines in Cancer and Immunotherapy.Cancers · 2021Review
- Gene-Edited Interleukin CAR-T Cells Therapy in the Treatment of Malignancies: Present and Future.Frontiers in immunology · 2021Review
- Lipid Metabolism in Tumor-Infiltrating T Cells.Advances in experimental medicine and biology · 2021Article
- Divergent Effect of Tacalcitol (PRI-2191) on Th17 Cells in 4T1 Tumor Bearing Young and Old Ovariectomized Mice.Aging and disease · 2020Article
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10 authors.
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Abstract
Tumor cell-derived molecules such as cytokines and lipid mediators play a critical role in inducing chronic inflammation in the tumor microenvironment. We found that Th17 cells were increased in the peripheral blood, spleen, and tumor tissues of mammary gland tumor-bearing mice. The Th17 cell survival factor, IL-23, was also overexpressed in tumor tissues isolated from mice and human breast cancer patients. Soluble molecules secreted from breast tumor cells, but not normal breast epithelial cells, induced IL-23 protein secretion in dendritic cells via induction of p19 mRNA expression. Our data further indicate that tumor-secreted PGE2 through EP2 and EP4 receptors enhanced IL-23 p19 gene transcription through binding to the cAMP-response element in the p19 promoter. Blocking PGE2 synthesis by NS398, a COX2 inhibitor, abrogated the enhancement of p19 expression both in vitro and in vivo. Furthermore, blocking protein kinase A (PKA) by H89 completely abrogated the inductive effects of tumor-conditioned medium and PGE2 on p19 transcription, whereas the cAMP active analog, Forskolin, mimics the PGE2 effect. Taken together, our results indicate that tumor-secreted PGE2 induces IL-23, but not IL-12, production in the tumor microenvironment, leading to Th17 cell expansion. This inductive effect of PGE2 on IL-23 p19 transcription is mediated through cAMP/PKA signaling transduction pathway.
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