Dendritic cell-tumor coculturing vaccine can induce antitumor immunity through both NK and CTL interaction

Immunization of dendritic cells (DC) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for prot ection and regression. We show here that immunization with bone marrow-deri ved DC cocultured with tumor cells can induce a protective immunity against challenges to viable tumor cells. In this study, we further investigated t he mechanism by which the antitumor activity was induced. Immunization of m ice with DC cocultured with murine colon carcinoma, CT-26 cells, augmented CTL activity against the tumor cells. Concomitantly, an increase in natural killer (NK) cell activity was also detected in the same mice. When DC were fixed with paraformaldehyde prior to coculturing with tumor cells, most of the CTL and NK cell activity diminished, indicating that DC are involved i n the process of presenting the tumor antigen(s) to CTL. NK cell depletion in vivo produced markedly low tumor-specific CTL activity responsible for t umor prevention. In addition, RT-PCR analysis confirmed the high expression of INF-gamma mRNA in splenocytes after vaccination with DC cocultured with tumors, but low expression in splenocytes from NK-depleted mice. Most impo rtantly, the tumor protective effect rendered to DC by the coculturing with CT-26 cells was not observed in NK-depleted mice, which suggests that DC c an induce an antitumor immune response by enhancing NK cell-dependent CTL a ctivation. Collectively, our results indicate that NK cells are required du ring the priming of cytotoxic T-cell response by DC-based tumor vaccine and seem to delineate a mechanism by which DC vaccine can provide the desired immunity, (C) 2001 Elsevier Science B.V. All rights reserved.