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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1342-1351. Prepublished online as a Blood First Edition Paper on October 13, 2005; DOI 10.1182/blood-2005-08-3485. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3485v1 107/4/1342    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 Fan, Z. Articles by Fu, Y.-X. Search for Related Content PubMed PubMed Citation Articles by Fan, Z. Articles by Fu, Y.-X. Related Collections Immunobiology Neoplasia Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY NK-cell activation by LIGHT triggers tumor-specific CD8+ T-cell immunity to reject established tumors Zusen Fan, Ping Yu, Yang Wang, Yugang Wang, May Lynne Fu, Wenhua Liu, Yonglian Sun, and Yang-Xin Fu From the National Laboratory of Biomacromolecules and Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; and the Department of Pathology, University of Chicago, Chicago, IL. Natural killer (NK) cells are generally reported as innate effector cells for killing virally infected and transformed cells. It is unclear how NK cells evoke adaptive immunity to eradicate tumors. We now demonstrate that the TNF superfamily member, LIGHT, known as TNFSF14 and a T-cell costimulatory molecule, is a critical ligand for the activation of NK cells. Herpesvirus entry mediator (HVEM) is expressed on NK cells, and its engagement with LIGHT mediates NK-cell activation. The expression of LIGHT inside tumors leads to rapid rejection in a NK-dependent manner. Both NK and CD8+ cells are essential but not sufficient for the rejection of tumors because mice lacking either population fail to reject the tumor. Interestingly, activated NK cells do not kill tumors directly but can facilitate the priming of tumor-specific CD8+ T cells in an IFN-–dependent manner. Conversely, intratumor depletion of either NK cells or IFN- during tumor progression disrupts CD8+ cell–mediated tumor rejection, suggesting that the tumor is the essential site for the crosstalk between NK and CD8+ cells. Furthermore, IFNG-deficient NK cells fail to effectively activate CD8+ T cells, suggesting IFN- plays an important role in NK-mediated activation of cytotoxic T lymphocytes (CTLs). Our findings establish a direct role for LIGHT in NK activation/expansion and a critical helper role of activated NK cells in priming CD8+ T cells and breaking T-cell tolerance at the tumor site. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. M'Hidi, M.-L. Thibult, B. Chetaille, F. Rey, R. Bouadallah, R. Nicollas, D. Olive, and L. Xerri High Expression of the Inhibitory Receptor BTLA in T-Follicular Helper Cells and in B-Cell Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia Am J Clin Pathol, October 1, 2009; 132(4): 589 - 596. [Abstract] [Full Text] [PDF] L. Wu, L. Wang, G. Hua, K. Liu, X. Yang, Y. Zhai, M. Bartlam, F. Sun, and Z. Fan Structural Basis for Proteolytic Specificity of the Human Apoptosis-Inducing Granzyme M J. Immunol., July 1, 2009; 183(1): 421 - 429. [Abstract] [Full Text] [PDF] G. Hua, S. Wang, C. Zhong, P. Xue, and Z. 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Lukashin, A. Ngam-ek, W. Zeng, N. Allaire, S. Perrin, et al. Targeting the Lymphotoxin-{beta} Receptor with Agonist Antibodies as a Potential Cancer Therapy Cancer Res., October 1, 2006; 66(19): 9617 - 9624. [Abstract] [Full Text] [PDF]

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