A bstract Im m u n izatio n w ith d en d ritic cells (D C s) p u lsed w ith tu m o r an tig en can activate tu m o r-sp ecific cytotoxic T lym pho cytes (C TL ), w h ich is respon sib le for tu m or protection and regressio n. In this study, w e exam ined w hether D C s pulsed w ith necrotic tum o r lysates can efficiently p revent m alignant m elanom a tum or cell m etastasis to the lung. D C s derived from m ouse bone m arrow w ere found to produce rem arkably elevated levels of IL-12 after

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... ing pulsed w ith the tum or lysates. M oreover, im m unization w ith these D C s induced C TL activation and protected m ice from m etastasis develop m en t b y intravenou sly inoculated tum or cells. In addition, these D C s activated N K cells in vitro in a contact-dependent m anner, an d indu ced N K activities in vivo . Fu rth erm o re, N K cell depletion befo re D C vaccinatio n sig nificantly redu ced the tum o r-specific C T L activity, IF N -γ pro duction, an d IF N -γinducible gene expression, and eventually interfered w ith th e an titu m o r effect o f tu m o r-p u lsed D C s. Finally, sim ilar findings w ith respect to N K cell depend en cy w ere obtained in th e C 57B L/ 6J-bg /bg m ice, w hich have severe deficiency in cytolytic activity o f N K cells. These data su ggest th at the antitu m or effect elicited b y D C vaccination, at least in a B 16 m elanom a m odel, requires the participation of both cytolytic N K and C D 8 T cells. T h e fin d in g s o f th is stu d y w o uld pro vid e im po rtant data fo r the effective d esign o f D C vaccines fo r cancer im m uno th erapy.