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Nat Commun. 2019 Mar 29;10(1):1424. doi: 10.1038/s41467-019-09416-2.

Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma.

Author information

1
S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
2
Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
3
S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA. george.miller@nyumc.org.
4
Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA. george.miller@nyumc.org.

Abstract

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-β, and induce FoxP3neg tumor-promoting IL-10+IL-17+IFNγregulatory CD4+ T cells. The balance between this distinctive TH program and canonical FoxP3TREGS 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.

PMID:
30926808
PMCID:
PMC6441038
DOI:
10.1038/s41467-019-09416-2
[Indexed for MEDLINE]
Free PMC Article

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