Elucidation of protumor/antitumor immune regulation mechanisms based on host versus cancer stem cell responses

基于宿主与癌症干细胞反应阐明促肿瘤/抗肿瘤免疫调节机制

• 批准号: 22300331
• 负责人: NISHIMURA Takashi
• 金额: $ 10.9万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22300331/
• 关键词: 癌幹細胞; IL-17; 腫瘍内微小環境; CD133; TGF-ss; TGF-b; TGF-β

In the present research, we investigated the mechanisms of protumor immune regulation in tumor microenvironment. As a result, we found that 〓 〓T cells were predominant IL-17-producing cells in tumor-bearing host, which promoted tumorigenesis through the angiogenesis. In addition, we demonstrated that the tumor-initiating capacity of CD133^+ cells was blocked by depleting Treg, which were induced in TGF-ss-dependent manner, suggesting that CD133^+ cancer initiating cells suppress CTL-mediated immunosurveillance. In the near future, overcoming the protumor immunity caused by cancer stem cells, which induces effective tumor-antigen specific Th1 cells, would be a promising strategy for cancer immunotherapy and prevention of recurrence.

在本研究中，我们探讨了肿瘤微环境中促肿瘤免疫调节的机制。结果发现，在荷瘤宿主中，〓〓T细胞是主要的IL-17产生细胞，通过血管生成促进肿瘤的发生。此外，我们还证明了CD133^+细胞的肿瘤启动能力被耗尽的Treg所阻断，而Treg是以转化生长因子-ss依赖的方式诱导的，这表明CD133^+肿瘤启动细胞抑制了CTL介导的免疫监视。在不久的将来，克服肿瘤干细胞诱导的肿瘤特异性Th1细胞的前肿瘤免疫，将是肿瘤免疫治疗和预防复发的一种有前景的策略。

项目成果

Toll-like receptor-dependent IL-12 production by dendritic cells is required for activation of natural killer cell-mediated Type-1 immunity induced by Chrysanthemum coronarium L.

• DOI: 10.1016/j.intimp.2010.11.026
• 发表时间: 2011-02
• 期刊: International immunopharmacology
• 影响因子: 5.6
• 作者: Sachi Tanaka;S. Koizumi;K. Masuko;N. Makiuchi;Y. Aoyagi;E. Quivy;R. Mitamura;Tsutomu Kano;T. Ohkuri;D. Wakita;K. Chamoto;H. Kitamura;T. Nishimura

Helper/killer hybrid epitope long peptide(H/K-HELP) as a novel tool for cancer vaccine therapy

辅助/杀伤杂合表位长肽（H/K-HELP）作为癌症疫苗治疗的新工具

• 发表时间: 2011
• 作者: Takahashi Y;Sakurai M;Murakami Y;et al.(11著者中、最終著者);上田龍三;西村孝司
• 通讯作者: 西村孝司

がん特異的免疫治療の進歩と細胞治療の問題点

癌症特异性免疫治疗的进展和细胞治疗的问题

• 发表时间: 2011
• 期刊: 腫瘍内科
• 作者: Kakimi K;Isobe M;Uenaka A;Wada H;Sato E;Doki Y;Nakajima J;Seto Y;Yamatsuji T;Naomoto Y;Shiraishi K;Takigawa N;Kiura K;Tsuji K;Iwatsuki K;Oka M;Pan L;Hoffman EW;Old LJ;Nakayama E;Suzuki S;西村孝司
• 通讯作者: 西村孝司

The extract of Japanese soybean, Kurosengoku activates the production of IL-12 and IFN-γ byDC or NK1.1(+) cells in a TLR4-andTLR2-dependent manner

日本大豆提取物黑五谷以 TLR4 和 TLR2 依赖性方式激活 DC 或 NK1.1(+) 细胞产生 IL-12 和 IFN-γ

• DOI: 10.1016/j.cellimm.2010.09.009
• 发表时间: 2011
• 期刊: Cell Immunol
• 影响因子: 4.3
• 作者: Tanaka S;Koizumi S;Makiuchi N;Aoyagi Y;Quivy E;Mitamura R;Kano T;Wakita D;Chamoto K;Kitamura H;Nishimura T
• 通讯作者: Nishimura T

Blockade of IL-6-signaling inhibits the pathogenesis of CD4+ T cell-mediated lethal graft-versus-host reaction against minor histocompatibility antigen.

• DOI: 10.1016/j.imlet.2011.01.004
• 发表时间: 2011-05
• 期刊: Immunology letters
• 影响因子: 4.4
• 作者: D. Noguchi;D. Wakita;T. Ohkuri;M. Tajima;K. Chamoto;H. Kitamura;T. Nishimura