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Blood, 15 July 2008, Vol. 112, No. 2, pp. 362-373. Prepublished online as a Blood First Edition Paper on March 19, 2008; DOI 10.1182/blood-2007-11-120998. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-11-120998v1 112/2/362    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Muranski, P. Articles by Restifo, N. P. Search for Related Content PubMed PubMed Citation Articles by Muranski, P. Articles by Restifo, N. P. Related Collections Immunobiology Neoplasia Immunotherapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Tumor-specific Th17-polarized cells eradicate large established melanoma Pawel Muranski1,*, Andrea Boni1,*, Paul A. Antony1,*, Lydie Cassard1, Kari R. Irvine1, Andrew Kaiser1, Chrystal M. Paulos1, Douglas C. Palmer1, Christopher E. Touloukian1, Krzysztof Ptak2, Luca Gattinoni1, Claudia Wrzesinski1, Christian S. Hinrichs1, Keith W. Kerstann1, Lionel Feigenbaum3, Chi-Chao Chan4, and Nicholas P. Restifo1 1 Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Mark O. Hatfield Clinical Research Center, Bethesda, MD; 2 National Institute of Neurological Disorders and Stroke, Bethesda, MD; 3 Science Applications International Corporation (SAIC), NCI, Frederick, MD; and 4 Laboratory of Immunology, National Eye Institute, Bethesda, MD CD4+ T cells can differentiate into multiple effector subsets, but the potential roles of these subsets in anti-tumor immunity have not been fully explored. Seeking to study the impact of CD4+ T cell polarization on tumor rejection in a model mimicking human disease, we generated a new MHC class II-restricted, T-cell receptor (TCR) transgenic mouse model in which CD4+ T cells recognize a novel epitope in tyrosinase-related protein 1 (TRP-1), an antigen expressed by normal melanocytes and B16 murine melanoma. Cells could be robustly polarized into Th0, Th1, and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles and by surface markers, suggesting the potential for differential effector function in vivo. Contrary to the current view that Th1 cells are most important in tumor rejection, we found that Th17-polarized cells better mediated destruction of advanced B16 melanoma. Their therapeutic effect was critically dependent on interferon- (IFN-) production, whereas depletion of interleukin (IL)–17A and IL-23 had little impact. Taken together, these data indicate that the appropriate in vitro polarization of effector CD4+ T cells is decisive for successful tumor eradication. This principle should be considered in designing clinical trials involving adoptive transfer–based immunotherapy of human malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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