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NK Dendritic Cells Expanded in IL-15 Exhibit Antitumor Responses In Vivo¹

Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

NK dendritic cells (NKDC) are a novel subtype of DC with NK cell properties. IL-15 is a pleiotropic cytokine that plays an obligate role in the proliferation and survival of NK cells. We hypothesized that IL-15 is also essential for NKDC development. NKDC were nearly absent in IL-15^–/– mice, but restored by administration of exogenous IL-15. Treatment of wild-type mice with IL-15 caused a 2- to 3-fold expansion of both NK cells and NKDC. After 7 days of culture with IL-15, sorted splenic NKDC expanded 10-fold while NK cells increased 5-fold. NKDC expanded in IL-15 retained their cytolytic capacity but lost the ability to stimulate naive T cells. Meanwhile, NKDC expanded in IL-15 produced 10 times more IFN- as fresh NKDC and conferred protection in a tumor prevention model. Thus, IL-15 is essential to the proliferation and survival of NKDC and IL-15 expanded NKDC possess antitumor properties.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R01 DK068346 and T32 CA09501 and the Charlotte Geyer Foundation.

² Address correspondence and reprint requests to Dr. Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center, Box 203, 1275 York Avenue, New York, NY 10021. E-mail address: dematter{at}mskcc.org

³ Abbreviations used in this paper: DC, dendritic cell; NKDC, natural killer DC; Flt3L, fms-like tyrosine kinase 3; _c, common -chain; CHO, Chinese hamster ovary; MHC I/II, MHC class I/II; IKDC, IFN--producing killer DC; pDC, plasmacytoid DC.

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