Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival
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 cell...
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Veröffentlicht in: | Nature medicine 2004-09, Vol.10 (9), p.942-949 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/nm1093 |