ArticleJournal for immunotherapy of cancer2019
The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 91 citations in OpenAlex.
- Conserved Metastatic Cell States and Spatial Immune Microenvironment Remodeling Define Pancreatic Cancer Liver Metastases.bioRxiv : the preprint server for biology · 2026Article
- Microplastics and nanoplastics-related genes signature predicts prognosis in pancreatic ductal adenocarcinoma and functional validation of interleukin 1 alpha.Translational cancer research · 2026Article
- Macrophage Plasticity: Phenotypic and Functional Profiles Across Pathological Microenvironments.International journal of molecular sciences · 2026Review
- The ASC-c isoform as a modulator of inflammasome activation: Insights into molecular mechanisms and therapeutic applications.The Journal of biological chemistry · 2026Article
- Cancer-Associated Fibroblasts: Clinical Applications in Imaging and Therapy.Tomography (Ann Arbor, Mich.) · 2025Review
- [PM2.5-induced M2 Polarization and IL-1α Secretion by Tumor-associated Macrophages Promotes Lung Adenocarcinoma Progression].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Cellular Cosmetics: How Innate Lymphoid Cells Can Recontour the Tumour Microenvironment.European journal of immunology · 2025Review
- Crosstalk between cancer‑associated fibroblasts and inflammation in tumor microenvironment: A novel perspective in cancer therapy (Review).Oncology reports · 2025Review
- Proteomics in pancreatic cancer.Biomarker research · 2025Review
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Inflammation in cancer: therapeutic opportunities from new insights.Molecular cancer · 2025Review
- Inflammation, microbiota, and pancreatic cancer.Cancer cell international · 2025Review
- Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.Journal of biomedical science · 2025Review
- TSLP: contrasting roles in cancer.Frontiers in immunology · 2025Review
- Thymic stromal lymphopoietin in leukemia: A double-edged sword?Leukemia research reports · 2025Review
- The Role of AIM2 in Cancer Development: Inflammasomes and Beyond.Journal of Cancer · 2025Review
- Blocking IL1RAP on cancer-associated fibroblasts in pancreatic ductal adenocarcinoma suppresses IL-1-induced neutrophil recruitment.Journal for immunotherapy of cancer · 2024Article
- Impact of Mitophagy-Related Genes on the Diagnosis and Development of Esophageal Squamous Cell Carcinoma via Single-Cell RNA-seq Analysis and Machine Learning Algorithms.Journal of microbiology and biotechnology · 2024Article
- Anakinra-Loaded Sphingomyelin Nanosystems Modulate In Vitro IL-1-Dependent Pro-Tumor Inflammation in Pancreatic Cancer.International journal of molecular sciences · 2024Article
- Identification of PANoptosis-related genes as prognostic indicators of thyroid cancer.Heliyon · 2024Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 4 countries.
Funding
Abstract
backgroundThe thymic stromal lymphopoietin (TSLP), a key cytokine for development of Th2 immunity, is produced by cancer associated fibroblasts (CAFs) in pancreatic cancer where predominant tumor infiltrating Th2 over Th1 cells correlates with reduced patients' survival. Which cells and molecules are mostly relevant in driving TSLP secretion by CAFs in pancreatic cancer is not defined.
methodsWe performed in vitro, in vivo and ex-vivo analyses. For in vitro studies we used pancreatic cancer cell lines, primary CAFs cultures, and THP1 cells. TSLP secretion by CAFs was used as a read-out system to identify in vitro relevant tumor-derived inflammatory cytokines and molecules. For in vivo studies human pancreatic cancer cells and CAFs were orthotopically injected in immunodeficient mice. For ex-vivo studies immunohistochemistry was performed to detect ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression in surgical samples. Bioinformatics was applied to interrogate published data sets.
resultsWe show in vitro that IL-1α and IL-1β released by pancreatic cancer cells and tumor cell-conditioned macrophages are crucial for TSLP secretion by CAFs. Treatment of immunodeficient mice orthotopically injected with human IL-1 positive pancreatic cancer cells plus CAFs using the IL-1R antagonist anakinra significantly reduced TSLP expression in the tumor. Importantly, we found that pancreatic cancer cells release alarmins, among which ASC, able to induce IL-1β secretion in macrophages. The relevance of ASC was confirmed ex-vivo by its expression in both tumor cells and tumor associated macrophages in pancreatic cancer surgical samples and survival data analyses showing statistically significant inverse correlation between ASC expression and survival in pancreatic cancer patients.
conclusionsOur findings indicate that tumor released IL-1α and IL-1β and ASC are key regulators of TSLP secretion by CAFs and their targeting should ultimately dampen Th2 inflammation and improve overall survival in pancreatic cancer.
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