Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival
| Autor: | George Coukos, Ben Daniel, Pui Cheng, Weiping Zou, Melina Evdemon-Hogan, Lieping Chen, Xavier Alvarez, Andrew A. Lackner, Linhua Zou, Lin Zhang, Mary L. Disis, Ilona Kryczek, Keith L. Knutson, Yun Zhu, Alan N. Gordon, Tyler J. Curiel, Matthew E. Burow, Shuang Wei, Peter Mottram, Leann Myers, Jose R. Conejo-Garcia |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
T-Lymphocytes chemical and pharmacologic phenomena Biology Lymphocyte Activation General Biochemistry Genetics and Molecular Biology Immunophenotyping Mice Interleukin 21 Immune privilege Cell Movement immune system diseases hemic and lymphatic diseases Animals Humans Cytotoxic T cell IL-2 receptor Chemokine CCL22 Ovarian Neoplasms Immunity Cellular Microscopy Confocal ZAP70 Ascites FOXP3 Peripheral tolerance Forkhead Transcription Factors Receptors Interleukin-2 hemic and immune systems Dendritic Cells General Medicine DNA-Binding Proteins Chemokines CC Immunology Interleukin 12 Female |
| Zdroj: | Nature Medicine. 10:942-949 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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