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*Substance via MeSH
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*Cancer Chemotherapy
The Journal of Immunology, 2003, 170: 1197-1201.
Copyright © 2003 by The American Association of Immunologists

The Contribution of NKT Cells, NK Cells, and Other {gamma}-Chain-Dependent Non-T Non-B Cells to IL-12-Mediated Rejection of Tumors 1

Se-Ho Park*,{dagger}, Tim Kyin*, Albert Bendelac2,* and Claude Carnaud*,{ddagger}

* Department of Molecular Biology, Princeton University, Princeton, NJ 08540; {dagger} Graduate School of Biotechnology, Korea University, Seoul, South Korea; and {ddagger} Institut National de la Santé et de la Recherche Medicale Unité 25 and E0209, Paris, France

IL-12 is a potent cytokine that impairs the growth of several tumors in vivo in natural as well as in therapeutic conditions. Although IL-12 can enhance a number of immunological antitumor mechanisms, including those mediated by NK cells and CTL, recent reports have suggested that the mouse CD1d-restricted V{alpha}14-J{alpha}18 NKT cell was the essential cell type recruited in most, if not all tumor rejection models, including the B16 melanoma. In this study, we have examined and compared the role of NKT cells, T cells, NK cells, and other non-T non-B cells in the rejection of B16 melanoma cells after exogenous administration of IL-12. Surprisingly, our results failed to confirm a necessary role for NKT cells in this model. Instead, we found that NK cells mediated the rejection of liver metastases, whereas other {gamma}c-dependent non-T non-B cells, possibly lymphoid dendritic cells, were required for rejection of skin tumors. These findings challenge the view that NKT cells are systematically required for IL-12-mediated rejection of tumors, and instead reveal that a variety of effector pathways can be recruited depending on the tumor microenvironment.




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