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Immunization with dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL), which is re-sponsible for tumor protection and regresion. In this study, we examined whether DCs pulsed with necrotic tumor lysates can efficiently pre-vent malignant melanoma tumor cel metastasis to the lung. DCs derived from mouse bone mar-row were found to produce remarkably elevated lysates. Moreover, imunization with these DCs induced CTL activation and protected mice from metastasis development by intravenously ino-culated tumor cells. In addition, these DCs acti-vated NK cells in vitro in a contact-dependent manner, and induced NK activities in vivo. Furthermore, NK cel depletion before DC vac-cination significantly reduced the tumor-speci-fic CTL activity, IFN-γ production, and IFN-γ- inducible gene expression, and eventually inter-DCs. Finaly, similar findings with respect to NK cel dependency were obtained in the C57BL/ 6J-bg/bg mice, which have severe deficiency in cytolytic activity of NK cels. These data sug-gest that the antitumor effect elicited by DC vaccination, at least in a B16 melanoma model, requires the participation of both cytolytic NK and CD8+T cells. The findings of this study would provide important data for the efective design of DC vaccines for cancer imunother-apy.

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