Basic research of cancer immunotherapy by using dendritic cells and clinical applications for head and neck tumors ; by using galactosylceramide

树突状细胞(DC)是一种特殊的APC，具有有效的抗肿瘤免疫应答。DC有望使用癌症免疫疗法。糖脂抗原α-半乳糖神经酰胺(α-GalCer)是由Ib类分子CD1d提呈的，能刺激Vα14 NKT细胞，快速诱导IL-4和干扰素-γ。我们研究了α-GalCer的抗肿瘤作用。我们还澄清了α-GalCer处理的DC在Vα14NKT缺陷小鼠中的抗肿瘤作用几乎被降低，这表明Vα14NKT细胞足以发挥这些抗肿瘤作用。在本项目中，我们在人体模型中详细地研究了α-GalCer的抗肿瘤作用。表型分析显示CD5 6+CD16 1+CD3+Vα2 4TCRNKT细胞在外周血单核细胞上扩增。这些结果表明，NKT细胞也是α-GalCer诱导人类模型肿瘤细胞凋亡的效应细胞。接下来，我们分析了口腔癌患者外周血单个核细胞对α-GalCer的反应。采集患者化疗前后外周血单个核细胞，观察NK、NKT细胞的变化。在本研究中，我们已向东北大学医院委员会申请临床应用，并获得批准。然后，我们已经开始收集临床样本，并获得了一些样本。但我们无法分析数据，因为样本数量并不多。我们希望继续收集癌症患者的样本，并通过使用α-GalCer治疗的DC来开发癌症免疫治疗。

Dendritic cells (DCs) are specialized APCs which have an effective antitumor immuno response. DCs are expected to using cancer immunotherapy. A glycolipid antigen, α-Galactosylceramide(α-GalCer) is presented by a class Ib molecule, CD1d, and stimulates V α14 NKT cells, resulting in a rapid induction of IL-4 and IFN-γ.We have investigated the antitumor effects of α-GalCer clarified that intratumoral onjection with α-GalCer treated-DCs resulted in regression of day 7 established poorly immunogenic tumors. We also clarified that these antitumor effects of α-GalCer treated-DCs were almost reduced in V α14NKT-deficient mice, suggesting that V α14 NKT cells are sufficient for these antitumor effects.In this project, we investigated the antitumor effects of α-GalCer in human model in detail. Phenotypic analysis revealed an expansion of CD56+ CD161+ CD3+Vα24 TCR NKTcells on PBMC. These results suggest that NKT cells are also effector cells for α-GalCer -induced tumor apoptosis on human model.Next, we analyzed a response to α-GalCer on PBMC from oral cancer patient. We collected patients' PBMC before and after chemotherapy, and investigated changes of NK or NKT cells. In this study, we have applied to committee of Tohoku University Hospital for the clinical application and were permitted. Then, we have started to collect clinical samples and got some samples. But we cannot analyze data because sample numbers were not so much. We hope that we will continue collecting samples from cancer patients and develop cancer immunotherapy by using α-GalCer treated-DCs.