Gamma-delta T cells stimulate IL-6 production by pancreatic stellate cells in pancreatic ductal adenocarcinoma
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| Titel: | Gamma-delta T cells stimulate IL-6 production by pancreatic stellate cells in pancreatic ductal adenocarcinoma |
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| Autoren: | Lena Seifert, Daniela Aust, Julian List, Max Heiduk, Janusz von Renesse, Adrian M. Seifert, Ann-Christin Meinecke, Rahel Decker, Jürgen Weitz, Thilo Welsch |
| Quelle: | J Cancer Res Clin Oncol |
| Verlagsinformationen: | Springer Science and Business Media LLC, 2020. |
| Publikationsjahr: | 2020 |
| Schlagwörter: | 0301 basic medicine, Carcinogenesis, Interleukin-6, Pancreatic Stellate Cells, Adenocarcinoma, Coculture Techniques, Extracellular Matrix, 3. Good health, Gene Expression Regulation, Neoplastic, 03 medical and health sciences, Gene Expression Regulation, Neoplastic [MeSH], Carcinoma, Pancreatic Ductal/immunology [MeSH], Cell Line, Tumor [MeSH], Cell Proliferation [MeSH], Original Article – Cancer Research, Humans [MeSH], Intraepithelial Lymphocytes/immunology [MeSH], Extracellular Matrix/genetics [MeSH], Pancreatic Stellate Cells/metabolism [MeSH], Pancreatic Stellate Cells/immunology [MeSH], Carcinoma, Pancreatic Ductal/genetics [MeSH], Carcinoma, Pancreatic Ductal/pathology [MeSH], Adenocarcinoma/pathology [MeSH], Adenocarcinoma/genetics [MeSH], Adenocarcinoma/immunology [MeSH], Interleukin-6/genetics [MeSH], Coculture Techniques [MeSH], Carcinogenesis/immunology [MeSH], Gamma-delta T cells, Tumor Microenvironment/genetics [MeSH], Carcinogenesis/genetics [MeSH], Pancreatic stellate cells, IL-6, Pancreatic cancer, Cell Line, Tumor, Tumor Microenvironment, Humans, Intraepithelial Lymphocytes, Carcinoma, Pancreatic Ductal, Cell Proliferation |
| Beschreibung: | Introduction The immunosuppressive tumor microenvironment promotes progression of pancreatic ductal adenocarcinoma (PDAC). γδ T cells infiltrate the pancreatic tumor stroma and support tumorigenesis through αβ T cell inhibition. Pancreatic stellate cell (PSC) activation contributes to pancreatic fibrosis in PDAC, limiting the delivery and efficacy of therapeutic agents. Whether γδ T cells have direct effects on PSC activation is unknown. Methods In this study, we analyzed tumor tissue from 68 patients with PDAC and determined the frequency and location of γδ T cells using immunohistochemistry and immunofluorescence. PDAC samples from the TCGA database with low and high TRGC2 expression were correlated with the expression of extracellular matrix genes. Further, PSCs were isolated from pancreatic tumor tissue and co-cultured with γδ T cells for 48 hours and cytokine production was measured using a cytometric bead array. Results γδ T cells infiltrated the pancreatic tumor stroma and were located in proximity to PSCs. A high infiltration of γδ T cells was associated with increased expression of several extracellular matrix genes in human PDAC. In vitro, γδ T cells stimulated IL-6 production by PDAC-derived PSCs. Conclusion γδ T cells activated PSCs and modulation of this interaction may enhance the efficacy of combinational therapies in human PDAC. |
| Publikationsart: | Article Other literature type |
| Sprache: | English |
| ISSN: | 1432-1335 0171-5216 |
| DOI: | 10.1007/s00432-020-03367-8 |
| Zugangs-URL: | https://link.springer.com/content/pdf/10.1007/s00432-020-03367-8.pdf https://pubmed.ncbi.nlm.nih.gov/32865617 https://www.ncbi.nlm.nih.gov/pubmed/32865617 https://link.springer.com/content/pdf/10.1007/s00432-020-03367-8.pdf https://europepmc.org/articles/PMC7679341/ https://pubmed.ncbi.nlm.nih.gov/32865617/ https://link.springer.com/article/10.1007/s00432-020-03367-8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679341 https://repository.publisso.de/resource/frl:6469386 |
| Rights: | CC BY |
| Dokumentencode: | edsair.doi.dedup.....5c1c59da9e2db052d8ce17afc3a61a3c |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Introduction The immunosuppressive tumor microenvironment promotes progression of pancreatic ductal adenocarcinoma (PDAC). γδ T cells infiltrate the pancreatic tumor stroma and support tumorigenesis through αβ T cell inhibition. Pancreatic stellate cell (PSC) activation contributes to pancreatic fibrosis in PDAC, limiting the delivery and efficacy of therapeutic agents. Whether γδ T cells have direct effects on PSC activation is unknown. Methods In this study, we analyzed tumor tissue from 68 patients with PDAC and determined the frequency and location of γδ T cells using immunohistochemistry and immunofluorescence. PDAC samples from the TCGA database with low and high TRGC2 expression were correlated with the expression of extracellular matrix genes. Further, PSCs were isolated from pancreatic tumor tissue and co-cultured with γδ T cells for 48 hours and cytokine production was measured using a cytometric bead array. Results γδ T cells infiltrated the pancreatic tumor stroma and were located in proximity to PSCs. A high infiltration of γδ T cells was associated with increased expression of several extracellular matrix genes in human PDAC. In vitro, γδ T cells stimulated IL-6 production by PDAC-derived PSCs. Conclusion γδ T cells activated PSCs and modulation of this interaction may enhance the efficacy of combinational therapies in human PDAC. |
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| ISSN: | 14321335 01715216 |
| DOI: | 10.1007/s00432-020-03367-8 |