TY - JOUR
T1 - Specialized dendritic cells induce tumor-promoting IL-10 + IL-17 + FoxP3 neg regulatory CD4 + T cells in pancreatic carcinoma
AU - Barilla, Rocky M.
AU - Diskin, Brian
AU - Caso, Raul Caso
AU - Lee, Ki Buom
AU - Mohan, Navyatha
AU - Buttar, Chandan
AU - Adam, Salma
AU - Sekendiz, Zennur
AU - Wang, Junjie
AU - Salas, Ruben D.
AU - Cassini, Marcelo F.
AU - Karlen, Jason
AU - Sundberg, Belen
AU - Akbar, Hashem
AU - Levchenko, Dmitry
AU - Gakhal, Inderdeep
AU - Gutierrez, Johana
AU - Wang, Wei
AU - Hundeyin, Mautin
AU - Torres-Hernandez, Alejandro
AU - Leinwand, Joshua
AU - Kurz, Emma
AU - Rossi, Juan A.Kochen
AU - Mishra, Ankita
AU - Liria, Miguel
AU - Sanchez, Gustavo
AU - Panta, Jyoti
AU - Loke, P’ng
AU - Aykut, Berk
AU - Miller, George
N1 - Funding Information:
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.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-09416-2
DO - 10.1038/s41467-019-09416-2
M3 - Article
C2 - 30926808
AN - SCOPUS:85063719241
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1424
ER -