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

Publication ,  Journal Article
Barilla, RM; Diskin, B; Caso, RC; Lee, KB; Mohan, N; Buttar, C; Adam, S; Sekendiz, Z; Wang, J; Salas, RD; Cassini, MF; Karlen, J; Sundberg, B ...
Published in: Nature Communications
March 29, 2019
Published version (DOI) Open Access Copy (Duke) Publisher Link

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-program. Specifically, CD11bCD103 DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3 tumor-promoting IL-10IL-17IFNγregulatory CD4 T cells. The balance between this distinctive T program and canonical FoxP3T is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This T-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11bCD103 DC promote CD4 T cell tolerance in PDA which may underscore its resistance to immunotherapy.

Duke Scholars

Berk Aykut
Author Berk Aykut  
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Published In

Nature Communications

DOI

10.1038/s41467-019-09416-2

EISSN

2041-1723

Publication Date

March 29, 2019

Volume

10

Issue

1

Publisher

Springer Science and Business Media LLC
 

Citation

APA
Chicago
ICMJE
MLA
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Barilla, R. M., Diskin, B., Caso, R. C., Lee, K. B., Mohan, N., Buttar, C., … Miller, G. (2019). Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-09416-2
Barilla, Rocky M., Brian Diskin, Raul Caso Caso, Ki Buom Lee, Navyatha Mohan, Chandan Buttar, Salma Adam, et al. “Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma.” Nature Communications 10, no. 1 (March 29, 2019). https://doi.org/10.1038/s41467-019-09416-2.
Barilla RM, Diskin B, Caso RC, Lee KB, Mohan N, Buttar C, et al. Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma. Nature Communications. 2019 Mar 29;10(1).
Barilla, Rocky M., et al. “Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma.” Nature Communications, vol. 10, no. 1, Springer Science and Business Media LLC, Mar. 2019. Crossref, doi:10.1038/s41467-019-09416-2.
Barilla RM, Diskin B, Caso RC, Lee KB, Mohan N, Buttar C, Adam S, Sekendiz Z, Wang J, Salas RD, Cassini MF, Karlen J, Sundberg B, Akbar H, Levchenko D, Gakhal I, Gutierrez J, Wang W, Hundeyin M, Torres-Hernandez A, Leinwand J, Kurz E, Rossi JAK, Mishra A, Liria M, Sanchez G, Panta J, Loke P, Aykut B, Miller G. Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma. Nature Communications. Springer Science and Business Media LLC; 2019 Mar 29;10(1).

Published In

Nature Communications

DOI

10.1038/s41467-019-09416-2

EISSN

2041-1723

Publication Date

March 29, 2019

Volume

10

Issue

1

Publisher

Springer Science and Business Media LLC