Immunoregulation of Dendritic Cell Subsets by Inhibitory Receptors in Urothelial Cancer.

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Version: Author's accepted manuscript
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_001B02D71DD0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Immunoregulation of Dendritic Cell Subsets by Inhibitory Receptors in Urothelial Cancer.
Journal
European urology
Author(s)
Chevalier M.F., Bohner P., Pieraerts C., Lhermitte B., Gourmaud J., Nobile A., Rotman S., Cesson V., Martin V., Legris A.S., Dartiguenave F., Gharbi D., De Leval L., Speiser D.E., Nardelli-Haefliger D., Jichlinski P., Derré L.
ISSN
1873-7560 (Electronic)
ISSN-L
0302-2838
Publication state
Published
Issued date
06/2017
Peer-reviewed
Oui
Volume
71
Number
6
Pages
854-857
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Blockade of inhibitory receptors (IRs) overexpressed by T cells can activate antitumor immune responses, resulting in the most promising therapeutic approaches, particularly in bladder cancer, currently able to extend patient survival. Thanks to their ability to cross-present antigens to T cells, dendritic cells (DCs) are an immune cell population that plays a central role in the generation of effective antitumor T-cell responses. While IR function and expression have been investigated in T cells, very few data are available for DCs. Therefore, we analyzed whether DCs express IRs that can decrease their functions. To this end, we investigated several IRs (PD-1, CTLA-4, BTLA, TIM-3, and CD160) in circulating CD1c javax.xml.bind.JAXBElement@4f1331d4 DCs, CD141 javax.xml.bind.JAXBElement@68e4feef DCs, and plasmacytoid DCs from healthy donors and patients with urothelial cancer (UCa). Different DC subsets expressed BTLA and TIM-3 but not other IRs. More importantly, BTLA and TIM-3 were significantly upregulated in DCs from blood of UCa patients. Locally, bladder tumor-infiltrating DCs also overexpressed BTLA and TIM-3 compared to DCs from paired nontumoral tissue. Finally, in vitro functional experiments showed that ligand-mediated engagement of BTLA and TIM-3 receptors significantly reduced the secretion of effector cytokines by DC subpopulations. Our findings demonstrate that UCa induces local and systemic overexpression of BTLA and TIM-3 by DCs that may result in their functional inhibition, highlighting these receptors as potential targets for UCa treatment.
We investigated the expression and function of a panel of inhibitory receptors in dendritic cells (DCs), an immune cell subpopulation critical in initiation of protective immune responses, among patients with urothelial carcinoma. We found high expression of BTLA and TIM-3 by blood and tumor DCs, which could potentially mediate decreased DC function. The results suggest that BTLA and TIM-3 might be new targets for urothelial carcinoma treatment.

Keywords
Biomarkers, Tumor/analysis, Case-Control Studies, Dendritic Cells/immunology, Dendritic Cells/pathology, Hepatitis A Virus Cellular Receptor 2/analysis, Humans, Phenotype, Receptors, Immunologic/analysis, Signal Transduction, Tumor Microenvironment, Up-Regulation, Urinary Bladder Neoplasms/immunology, Urinary Bladder Neoplasms/pathology, Urothelium/immunology, Urothelium/pathology, BTLA, Dendritic cells, Inhibitory receptors, TIM-3, Urothelial cancer
Pubmed
Web of science
Open Access
Yes
Create date
10/03/2017 14:43
Last modification date
20/08/2019 12:22
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