Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells.

Details

Serval ID
serval:BIB_7B26C9A25D39
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells.
Journal
Cancer Research
Author(s)
Conrad C., Gregorio J., Wang Y.H., Ito T., Meller S., Hanabuchi S., Anderson S., Atkinson N., Ramirez P.T., Liu Y.J., Freedman R., Gilliet M.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Publication state
Published
Issued date
2012
Volume
72
Number
20
Pages
5240-5249
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Despite its immunogenicity, effective antitumor responses are limited, due, in part, to the presence of forkhead box protein 3-positive (Foxp3(+)) T regulatory (Treg) cells in the tumor microenvironment. However, the mechanisms that regulate the accumulation and the suppressive function of these Foxp3(+) Treg cells are poorly understood. Here, we found that the majority of Foxp3(+) Treg cells accumulating in the tumor microenvironment of EOCs belong to the subset of Foxp3(+) Treg cells expressing inducible costimulator (ICOS). The expansion and the suppressive function of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC). Accordingly, ICOS(+) Foxp3(+) Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS(+) Foxp3(+) Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS(+) Treg cell subset being a stronger predictor than total Foxp3(+) Treg cells. These findings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS(+) Foxp3(+) Treg cells, leading to tumor progression in ovarian cancer.
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2012 18:52
Last modification date
20/08/2019 14:37
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