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 T H -program. Specifically, CD11b + CD103 − DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3 neg tumor-promoting IL-10 + IL-17 + IFNγ + regulatory CD4 + T cells. The balance between this distinctive T H program and canonical FoxP3 + T REGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This T H -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.
Original language | English |
---|---|
Article number | 1424 |
Journal | Nature Communications |
Volume | 10 |
Issue number | 1 |
DOIs | |
State | Published - Dec 1 2019 |
Bibliographical note
Publisher Copyright:© 2019, The Author(s).
Funding
Cell sorting/flow cytometry technologies were provided by NYU Langone’s Cytometry and Cell Sorting Laboratory, which is supported in part by grant P30CA016087 from the National Institutes of Health/National Cancer Institute. The results published here are in part based upon data generated by the TCGA Research Network: https://www.cancer. gov/tcga.
Funders | Funder number |
---|---|
National Institutes of Health/National Cancer Institute | |
National Childhood Cancer Registry – National Cancer Institute | T32CA193111 |
Department of Psychiatry, Columbia University Irving Medical Center, New York, USA; New York State Psychiatric Institute, New York, USA | P30CA016087 |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy