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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 2, 2007 Accepted March 10, 2008 Tumor-specific Th17-polarized cells eradicate large established melanoma Pawel Muranski*, Andrea Boni, Paul A Antony, Lydie Cassard, Kari R Irvine, Andrew Kaiser, Chrystal M Paulos, Douglas C Palmer, Christopher E Touloukian, Krzysztof Ptak, Luca Gattinoni, Claudia Wrzesinski, Christian S Hinrichs, Keith Kerstann, Lionel Feigenbaum, Chi-Chao Chan, and Nicholas P Restifo Center for Cancer Research, National Cancer Institute, National Institutes of Health, Mark O. Hatfield Clinical Research Center, Bethesda, MD, United States National Institute of Neurological Disease and Stroke, NIH, Bethesda, MD, United States Science Applications International Corporation, National Cancer Institute, NIH, Frederick, MD, United States Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD, United States * Corresponding author; email: muranskp{at}mail.nih.gov. 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. We sought to study the impact of CD4+ T cell polarization on efficacy of tumor rejection in a model closely mimicking human disease where the target antigens are often non-mutated tissue differentiation self-antigens. 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 that is expressed by normal melanocytes and B16 murine melanoma. We found that cells could be robustly polarized into Th0, Th1 and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles as well as by surface markers, suggesting the potential for differential effector function in vivo. Contrary to the current view that Th1 cells play the most important role in tumor rejection, we found that Th17-polarized cells were superior in mediating destruction of advanced B16 melanoma. Unexpectedly, their therapeutic effect was critically dependent on IFN- production, while depletion of 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 the successful tumor eradication. This principle should be taken under consideration in the design of future clinical trials involving adoptive transfer-based immunotherapy of human malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Th17 and cancer: friends or foes? Vincenzo Bronte Blood 2008 112: 214. [Full Text] [PDF] This article has been cited by other articles: H.-R. Yen, T. J. Harris, S. Wada, J. F. Grosso, D. Getnet, M. V. Goldberg, K.-L. Liang, T. C. Bruno, K. J. Pyle, S.-L. Chan, et al. Tc17 CD8 T Cells: Functional Plasticity and Subset Diversity J. Immunol., December 1, 2009; 183(11): 7161 - 7168. [Abstract] [Full Text] [PDF] M. L. Disis Enhancing Cancer Vaccine Efficacy via Modulation of the Tumor Microenvironment Clin. Cancer Res., November 1, 2009; 15(21): 6476 - 6478. [Abstract] [Full Text] [PDF] G. Murugaiyan and B. Saha Protumor vs Antitumor Functions of IL-17 J. Immunol., October 1, 2009; 183(7): 4169 - 4175. 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