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

我们已经报道了肿瘤内注射α-半乳糖神经酰胺（α-GalCer）处理的树突状细胞（DCs）选择性地激活自然杀伤T细胞（NKT细胞），导致第7天建立的免疫原性差的肿瘤消退。为了阐明DCs产生的IL-12的作用，从IL-12缺陷小鼠收获的α-GalCer处理的DCs可以像使用WT的DCs一样强烈地抑制MCA 205肿瘤生长。有趣的是，α-GalCer注射不能增强从IFN-γ缺陷小鼠收获的淋巴细胞的体外细胞毒性。此外，在IFN-γ缺陷小鼠中使用经α-GalCer处理的DC的抗肿瘤活性完全受损。这些结果表明IFN-γ在α-GalCer处理的DC的这些抗肿瘤反应中起关键作用，而IL-12在α-GalCer处理的DC的这些抗肿瘤反应中起关键作用。表型分析显示PBMC上CD 3 + CD 161 + CD 56- Vα 24 TCR + T细胞扩增。这些结果与先前的报道一致，表明α-GalCer选择性激活小鼠中的Vα 14 NKT细胞，表明瘤内注射α-GalCer处理的DC应被认为是产生对人的抗肿瘤应答和进一步用于头颈部肿瘤的临床应用的可行策略。

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.