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

我们已经报道，用α半乳糖神经酰胺(αGalCer)处理的树突状细胞(DC)瘤内注射选择性地激活自然杀伤T细胞(NKT细胞)，导致第7天建立的免疫原性较差的肿瘤消退。为了阐明DC产生IL-12的作用，从IL-12缺陷小鼠获取的α-GalCer处理的DC可以像使用WT的DC一样抑制肿瘤生长。有趣的是，α-GalCer注射并不能增强干扰素-γ缺陷小鼠淋巴细胞的体外细胞毒作用。此外，用α-GalCer处理的DC对干扰素-γ缺陷小鼠的抗肿瘤活性也受到了明显的损害。这些结果表明，干扰素-γ而不是IL-12在α-GalCer处理的DC的这些抗肿瘤反应中起关键作用。接下来，我们研究了αGalCer对人外周血单个核细胞的抗肿瘤作用。表型分析显示CD3+CD16 1+CD5 6-Vα2 4TCR+T细胞在单个核细胞上呈扩增状态。这些结果与先前报道的α-GalCer选择性激活小鼠V-α14NKT细胞的结果一致，提示瘤内注射α-GalCer处理的DC可以被认为是在人类身上产生抗肿瘤反应以及进一步临床应用于头颈部肿瘤的可行策略。

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.