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Blood, 6 August 2009, Vol. 114, No. 6, pp. 1141-1149. Prepublished online as a Blood First Edition Paper on May 21, 2009; DOI 10.1182/blood-2009-03-208249.
PLENARY PAPER Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environmentsDepartments of 1 Surgery and 2 Biostatistics, University of Michigan, Ann Arbor; 3 Division of Gynecologic Oncology, Tulane University, New Orleans, LA; 4 Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia; and 5 Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor
Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1β (IL-1β), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-
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| Copyright © 2009 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immune-boosting strategies based on promoting the Th17 cell population in cancer patients. 
