Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma.
Nat Commun
; 10(1): 1424, 2019 03 29.
Article
em En
| MEDLINE
| ID: mdl-30926808
The drivers and the specification of CD4+ T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique TH-program. Specifically, CD11b+CD103- DC predominate in PDA, express high IL-23 and TGF-ß, and induce FoxP3neg tumor-promoting IL-10+IL-17+IFNγ+ regulatory CD4+ T cells. The balance between this distinctive TH program and canonical FoxP3+ TREGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This TH-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b+CD103- DC promote CD4+ T cell tolerance in PDA which may underscore its resistance to immunotherapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Células Dendríticas
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Interleucina-10
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Linfócitos T Reguladores
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Interleucina-17
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article