Gamma-delta T cells stimulate IL-6 production by pancreatic stellate cells in pancreatic ductal adenocarcinoma.
Adenocarcinoma
/ genetics
Carcinogenesis
/ genetics
Carcinoma, Pancreatic Ductal
/ genetics
Cell Line, Tumor
Cell Proliferation
Coculture Techniques
Extracellular Matrix
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Interleukin-6
/ genetics
Intraepithelial Lymphocytes
/ immunology
Pancreatic Stellate Cells
/ immunology
Tumor Microenvironment
/ genetics
Gamma-delta T cells
IL-6
Pancreatic cancer
Pancreatic stellate cells
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
03
07
2020
accepted:
18
08
2020
pubmed:
1
9
2020
medline:
15
12
2020
entrez:
1
9
2020
Statut:
ppublish
Résumé
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. 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. 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. γδ T cells activated PSCs and modulation of this interaction may enhance the efficacy of combinational therapies in human PDAC.
Identifiants
pubmed: 32865617
doi: 10.1007/s00432-020-03367-8
pii: 10.1007/s00432-020-03367-8
pmc: PMC7679341
doi:
Substances chimiques
Interleukin-6
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3233-3240Subventions
Organisme : Deutsche Forschungsgemeinschaft (DE)
ID : SE-2980/5-1
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