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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1313-1319. Prepublished online as a Blood First Edition Paper on April 18, 2006; DOI 10.1182/blood-2005-11-011320. This Article Full Text (PDF) All Versions of this Article: blood-2005-11-011320v1 108/4/1313    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 Sutherland, C. L Articles by Cosman, D. Search for Related Content PubMed PubMed Citation Articles by Sutherland, C. L Articles by Cosman, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 2, 2005 Accepted April 9, 2006 ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity; enhancement by IL-15 Claire L Sutherland*, Brian Rabinovich, N Jan Chalupny, Pierre Brawand, Robert Miller, and David Cosman Department of Oncology, Amgen Inc., Seattle, WA, USA * Corresponding author; email: sutherlc{at}amgen.com. ULBPs are human ligands for NKG2D, an activating receptor expressed on NK, NK1.1+ T cells and T cells. ULBPs are expressed by a variety of leukemias, carcinomas, melanomas and tumor cell lines. ULBP expression correlates with improved survival in cancer patients, however, the nature of the immune response that ULBPs elicit is not well understood. We report that ectopic expression of ULBP1 or ULBP2 on murine EL4 or RMA tumor cells elicits potent anti-tumor responses in syngeneic C57BL/6 and SCID mice. Although binding of ULBP3 to murine NKG2D could not be demonstrated in vitro, ULBP3 can also stimulate anti-tumor responses, suggesting that ULBP3 binds to murine NKG2D or possibly another receptor in vivo. ULBP expression was found to recruit NK, NK1.1+ T cells and T cells to the tumor. IL-15 was found to strongly enhance the immune response directed against ULBP-expressing tumors. Tumors can evade NKG2D immunity by downregulating expression of NKG2D. Our data suggest that IL-15 may be useful for overcoming this tumor evasion strategy. Together, these results demonstrate that ULBP expression can elicit a potent immune response and suggest that ULBPs, alone or in combination with IL- 15, can be exploited for anti-tumor therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Carlsten, H. Norell, Y. T. Bryceson, I. Poschke, K. Schedvins, H.-G. Ljunggren, R. Kiessling, and K.-J. 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