An analysis for mechanism of antitumor effects of dendritic cells treated with αGalactosylceramide

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We have already reported that intratumoral injection of dendritic cells (DCs) treated with αGalactosylceramide (αGalCer) selectively activated natural killer T cells (NKT cells), resulting in regression of day 7 established poorly immunogenic tumors.To clarify a role of IL-12 produced by DCs, α-GalCer treated-DCs harvested from IL-12 deficient mice can inhibits MCA205 tumor growth as strong as using WT's DCs. Interestingly, α-GalCer injection can not enhance the in vitro cytotoxicity of lymphocytes harvested from IFN-γ-deficient mice. Furthermore, the antitumor activity of using DCs treated with α-GalCer in IFN-γ-deficient mice is impaired comopletely. These results indicate that IFN-γ, but IL-12, plays critical role in these antitumor response of α-GalCer treated-DCs.Next, we investigated the antitumor effects of αGalCer on human peripheral blood mononuclear cells (PBMC). Phenotypic analysis revealed an expansion of CD3+ CD161+ CD56- Vα24TCR+ T cells on PBMC. These results are consistent with the previous reports showing that α-GalCer selectively activates Vα14NKT cells in mice, suggesting that intratumoral injection of α-GalCer treated-DC should be considered a viable strategy for the generation of antitumor responses on human and for further clinical applications for head and neck tumors.