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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Rocky M. Barilla, Brian Diskin, Raul Caso Caso, Ki Buom Lee, Navyatha Mohan, Chandan Buttar, Salma Adam, Zennur Sekendiz, Junjie Wang, Ruben D. Salas, Marcelo F. Cassini, Jason Karlen, Belen Sundberg, Hashem Akbar, Dmitry Levchenko, Inderdeep Gakhal, Johana Gutierrez, Wei Wang, Mautin Hundeyin, Alejandro Torres-Hernandez, Joshua Leinwand, Emma Kurz, Juan A. Kochen Rossi, Ankita Mishra, Miguel Liria, Gustavo Sanchez, Jyoti Panta, P’ng Loke, Berk Aykut, George Miller

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+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. More... »

PAGES

1424

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

10

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-09416-2

DOI

http://dx.doi.org/10.1038/s41467-019-09416-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113058613

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30926808


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