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Blood, 15 January 2005, Vol. 105, No. 2, pp. 721-727. Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2003-12-4187. This Article Full Text (PDF) All Versions of this Article: 2003-12-4187v1 105/2/721    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 Kobayashi, H. Articles by Tagaya, Y. Search for Related Content PubMed PubMed Citation Articles by Kobayashi, H. Articles by Tagaya, Y. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 8, 2003 Accepted August 29, 2004 The role of trans-cellular IL-15-presentation in the activation of NK-mediated killing, which leads to enhanced tumor immunesurveillance Hisataka Kobayashi, Sigrid Dubois, Noriko Sato, Helen Sabzevari, Yoshio Sakai, Thomas A Waldmann, and Yutaka Tagaya* Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: ytagaya{at}helix.nih.gov. IL-15 is a critical factor for the proliferation and activation of NK and CD8 T cells. Recently we demonstrated that IL-15R expressed on monocytes/dendritic cells captures and presents IL-15 to neighboring cells in trans (trans-presentation of IL-15) through cell-cell contact. In the current study, we provide evidence that the IL-15 presented in trans, but not soluble IL-15 at physiological concentrations, augments the killing activity mediated by NK cells in vitro. In addition, transfection of IL-15Rinto a colon carcinoma cell line (MC38) enabled these cells to present IL-15 in trans to NK cells and augmented their killing activity, resulting in the efficient lysis of MC38 cells by NK cells in vitro. Furthermore, these transfected MC38 cells no longer form fatal pulmonary metastases in mice. It was also shown that NK cells playan important role in the rejection of MC38 cells under these circumstances. in IL-15 transgenic mice. These results collectively suggest that the IL-15 trans-presentation mechanism operates in vivo to augment the tumor immune surveillance mechanism. Furthermore, our observation provides the scientific basis for a novel strategy to prevent cancer development/metastasis. 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