| First Author | Barilla RM | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 1424 |
| PubMed ID | 30926808 | Mgi Jnum | J:273330 |
| Mgi Id | MGI:6286866 | Doi | 10.1038/s41467-019-09416-2 |
| Citation | Barilla RM, et al. (2019) Specialized dendritic cells induce tumor-promoting IL-10(+)IL-17(+) FoxP3(neg) regulatory CD4(+) T cells in pancreatic carcinoma. Nat Commun 10(1):1424 |
| abstractText | 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-beta, and induce FoxP3(neg) tumor-promoting IL-10(+)IL-17(+)IFNgamma(+ )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. |
