Interleukin-18 activates Natural Killer cells and induces tumor apoptosis ; clinical applications for head and neck tumors.

Interleukin-18激活自然杀伤细胞并诱导肿瘤细胞凋亡；

基本信息

批准号：
14370655
负责人：
ECHIGO Seishi
金额：
$ 7.36万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370655/
关键词：
IL-18 antitumor natural killer cells IFN-γ apoptosis dendriticcells innate immunity specific immunity

项目摘要

We have investigated the antitumor effects of IL-18 in marine and human models and reported that IL-18 activated natural killer cells and induced tumor apoptosis. Moreover, tumor apoptosis induced tumor specific cytotoxic T lymphocytes (CTL) by using dendritic cells.We investigated the antitumor effects of combining IL-18 and IL-2 on human peripheral blood mononuclear cells. The combination of these two cytokines produced a large amount of IFN-γ and enhanced tumor cell death against tumor cell lines. Moreover, phenotypic analysis revealed an expansion of CD56+ CD161+ CD3-NK cells on PBMC.In this project, we investigated the antitumor effects of IL-18 in human model in detail. We revealed that co-culture with tumor cells and PBMC activated by IL-2 and IL-18 induced tumor apoptosis on human squamous cell carcinoma cell line. Next, we examined the expression of TRAIL and FasL on IL-18-stimulated PBMC by using RT PCR and revealed that TRAIL and FasL mRNA were upregulated by IL-18 stimulation. These results suggest that TRAIL and FasL play critical role for IL-18-induced tumor apoptosis.Next, we analyzed a response to IL-18 on PBMC from oral cancer patient. We collected patients' PBMC before and after chemotherapy, and investigated changes of NK or T 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 IL-18.

我们在海洋和人类模型中研究了 IL-18 的抗肿瘤作用，并报道 IL-18 激活自然杀伤细胞并诱导肿瘤细胞凋亡，此外，肿瘤细胞凋亡通过使用树突状细胞诱导肿瘤特异性细胞毒性 T 淋巴细胞 (CTL)。 IL-18和IL-2联合对人外周血单核细胞的抗肿瘤作用这两种细胞因子的联合产生了大量的IFN-γ并增强了针对肿瘤细胞系的肿瘤细胞死亡。揭示了 PBMC 上 CD56+ CD161+ CD3-NK 细胞的扩增。在这个项目中，我们详细研究了 IL-18 在人类模型中的抗肿瘤作用，我们揭示了与肿瘤细胞和由 IL-2 和 IL 激活的 PBMC 共培养。 -18 诱导人鳞状细胞癌细胞系的肿瘤细胞凋亡接下来，我们通过 RT PCR 检测了 TRAIL 和 FasL 在 IL-18 刺激的 PBMC 上的表达，并揭示了 TRAIL 和 FasL 的表达。 FasL mRNA 通过 IL-18 刺激上调，表明 TRAIL 和 FasL 在 IL-18 诱导的肿瘤细胞凋亡中发挥关键作用。接下来，我们分析了口腔癌患者的 PBMC 对 IL-18 的反应。化疗前后的PBMC，并调查NK或T细胞的变化。本研究已向东北大学医院委员会申请并获得批准，然后开始收集临床样本并获得了一些。但我们无法分析数据，因为样本数量并不多，我们希望继续从癌症患者身上收集样本，并利用IL-18开发癌症免疫疗法。