Ag-presenting CpG-activated pDCs prime Th17 cells that induce tumor regression.

Details

Serval ID
serval:BIB_A2B80E4B8BB3
Type
Article: article from journal or magazin.
Collection
Publications
Title
Ag-presenting CpG-activated pDCs prime Th17 cells that induce tumor regression.
Journal
Cancer research
Author(s)
Guéry L., Dubrot J., Lippens C., Brighouse D., Malinge P., Irla M., Pot C., Reith W., Waldburger J.M., Hugues S.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Publication state
Published
Issued date
15/11/2014
Peer-reviewed
Oui
Volume
74
Number
22
Pages
6430-6440
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Plasmacytoid dendritic cells (pDC) rapidly and massively produce type I IFN and other inflammatory cytokines in response to foreign nucleic acids, thereby indirectly influencing T-cell responses. Moreover, antigen (Ag)-presenting pDCs directly regulate T-cell differentiation. Depending on the immune environment, pDCs exhibit either tolerogenic or immunogenic properties. Here, we show that CpG-activated pDCs promote efficient Th17 differentiation. Indeed, Th17 responses are defective in mice selectively lacking MHCII on pDCs upon antigenic challenge. Importantly, in those mice, the frequency of Th17 cells infiltrating solid tumors is impaired. As a result, the recruitment of infiltrating leukocytes in tumors, including tumor-specific cytotoxic T lymphocytes (CTL), is altered and results in increased tumor growth. Importantly, following immunization with tumor Ag and CpG-B, MHCII-restricted Ag presentation by pDCs promotes the differentiation of antitumor Th17 cells that induce intratumor CTL recruitment and subsequent regression of established tumors. Our results highlight a new role for Ag presenting activated pDCs in promoting the development of Th17 cells and impacting on antitumor immunity.
Keywords
Amino Acid Sequence, Animals, Antigen Presentation, Dendritic Cells/physiology, Dinucleoside Phosphates/immunology, Histocompatibility Antigens Class II/immunology, Immunization, Immunotherapy, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Neoplasms, Experimental/immunology, T-Lymphocytes, Cytotoxic/physiology, Th17 Cells/immunology
Pubmed
Web of science
Open Access
Yes
Create date
21/08/2018 15:57
Last modification date
20/08/2019 15:08
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