Identification of new molecule for regulatory T cells in an anti-tumor immunity

• Project/Area Number: 15H06880
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Nagoya University (2016); National Cancer Center Japan (2015)
• Principal Investigator: Sugiyama Daisuke 名古屋大学, 医学系研究科, 研究員 (90759375)
• Research Collaborator: Nishikawa Hiroyoshi 名古屋大学, 大学院医学系研究科・分子細胞免疫学, 教授 (10444431) ; Doi Toshihiko 国立がん研究センター先端医療開発センター免疫TR分野, 先端医療科長 (20522907)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 制御性T細胞 / Human immunology / 腫瘍浸潤リンパ球 / Human Immunology / 免疫学 / 癌 / トランスレーショナルリサーチ / ヒト研究 / CD8陽性T細胞

Outline of Final Research Achievements

A cancer immunotherapy using the immune systems attracts attention as a therapeutic method to novel cancer therapy. In this study, we analyzed immune responses of the stomach-cancer patient and was intended that we got knowledge to be connected for development of the new cancer immunotherapy.
After analyzing the immune cells in a blood or tumor tissue of the stomach cancer patients, there were more ratios of regulatory T cells which suppressed anti-tumor immune responses in the tumor tissues than blood, and they highly expressed cell surface molecules such as ICOS or CTLA-4. From these results, we suggested that expect an improvement effect of the anti-tumor immune responses by the removal of the regulatory T cells by ICOS and CTLA-4 marker.

Research Products

• [Journal Article] Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. (2016)
  • Author(s): Saito, T., Nishikawa, H., Wada, H., Nagano, Y., Sugiyama, D., Atarashi, K., Maeda, Y., Hamaguchi, M., Ohkura, N., Sato, E., Nagase, H., Nishimura, J., Yamamoto, H., Takiguchi, S., Tanoue, T., Suda, W., Morita, H., Hattori, M., Honda, K., Mori, M., Doki, Y., Sakaguchi, S.
  • Journal Title: Nat. Med Volume: 22 Issue: 6 Pages: 679-684
  • DOI: 10.1038/nm.4086
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fecal microbiota transplantation for patients with steroid-resistant/dependent acute graft-versus-host disease of the gut (2016)
  • Author(s): Kakihana K, Fujioka Y, Suda W, Najima Y, Kuwata G, Sasajima S, Mimura I, Morita H, Sugiyama D, Nishikawa H, Hattori M, Hino Y, Ikegawa S, Yamamoto K, Toya T, Doki N, Koizumi K, Honda K, Ohashi K
  • Journal Title: Blood Volume: 128 Issue: 16 Pages: 2083-2088
  • DOI: 10.1182/blood-2016-05-717652
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Regulatory T-cell induced anergic CD8+ T cells with suppressive function are novel targets of anti-CTLA-4 mAb (2016)
  • Author(s): Danbee Ha, Hiroyoshi Nishikawa, Daisuke Sugiyama, Yuka Maeda, Dennis Adeegbe, Eichi Sato, Atsushi Tanemura, Ichiro Katayama, Shimon Sakaguchi
  • Organizer: 第75回日本癌学会
  • Place of Presentation: パシフィコ横浜