Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.

Details

Serval ID
serval:BIB_DF9221D8DB57
Type
Article: article from journal or magazin.
Collection
Publications
Title
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.
Journal
Nature Medicine
Author(s)
Curiel T.J., Coukos G., Zou L., Alvarez X., Cheng P., Mottram P., Evdemon-Hogan M., Conejo-Garcia J.R., Zhang L., Burow M., Zhu Y., Wei S., Kryczek I., Daniel B., Gordon A., Myers L., Lackner A., Disis M.L., Knutson K.L., Chen L., Zou W.
ISSN
1078-8956 (Print)
ISSN-L
1078-8956
Publication state
Published
Issued date
2004
Volume
10
Number
9
Pages
942-949
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Abstract
Regulatory T (T(reg)) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by T(reg) cells; however, definitive evidence that T(reg) cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4(+)CD25(+)FOXP3(+) T(reg) cells in 104 individuals affected with ovarian carcinoma, that human tumor T(reg) cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo. We also show that tumor T(reg) cells are associated with a high death hazard and reduced survival. Human T(reg) cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T(reg) cells to the tumor. This specific recruitment of T(reg) cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T(reg) cell migration or function may help to defeat human cancer.
Keywords
Animals, Ascites/immunology, CD4-Positive T-Lymphocytes, Cell Movement/immunology, Chemokine CCL22, Chemokines, CC/immunology, Chemokines, CC/metabolism, DNA-Binding Proteins, Dendritic Cells/immunology, Female, Forkhead Transcription Factors, Humans, Immunity, Cellular/immunology, Immunophenotyping, Lymphocyte Activation/immunology, Mice, Microscopy, Confocal/methods, Ovarian Neoplasms/immunology, Receptors, Interleukin-2, T-Lymphocytes/immunology
Pubmed
Web of science
Create date
14/10/2014 12:43
Last modification date
20/08/2019 17:03
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