Nature Medicine
10, 942 - 949 (2004)
Published online: 22 August 2004; | doi:10.1038/nm1093
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survivalTyler J Curiel1, George Coukos2, Linhua Zou1, Xavier Alvarez1, Pui Cheng1, Peter Mottram1, Melina Evdemon-Hogan1, Jose R Conejo-Garcia2, Lin Zhang2, Matthew Burow1, Yun Zhu1, Shuang Wei1, Ilona Kryczek1, Ben Daniel1, Alan Gordon3, Leann Myers1, Andrew Lackner1, Mary L Disis4, Keith L Knutson4, Lieping Chen5
& Weiping Zou11
Tulane University Health Science Center, New Orleans, Louisiana 70112, USA. 2
Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. 3
Baylor University Medical Center, Dallas, Texas 75249, USA. 4
Division of Oncology, University of Washington, Seattle, Washington 98195, USA. 5
Department of Dermatology, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Correspondence should be addressed to Weiping Zou wzou@tulane.eduRegulatory T (Treg) 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 Treg cells; however, definitive evidence that Treg cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4+CD25+FOXP3+ Treg cells in 104 individuals affected with ovarian carcinoma, that human tumor Treg cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo. We also show that tumor Treg cells are associated with a high death hazard and reduced survival. Human Treg 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 Treg cells to the tumor. This specific recruitment of Treg cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking Treg cell migration or function may help to defeat human cancer.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
