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Development of new cancer immunotherapy that targets the CD69-Myl9/12 system

Research Project

Project/Area Number 18K07257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionChiba University

Principal Investigator

Nasu Ryo  千葉大学, 大学院医学研究院, 特任助教 (30466859)

Co-Investigator(Kenkyū-buntansha) 岩立 康男  千葉大学, 大学院医学研究院, 教授 (70272309)
本橋 新一郎  千葉大学, 大学院医学研究院, 教授 (60345022)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsがん免疫 / CD69 / 細胞傷害性T細胞 / 免疫チェックポイント阻害剤 / 免疫逃避機構
Outline of Final Research Achievements

The purpose of this study is to develop a new cancer immunotherapy that targets the CD69-Myl9/12 system. Myl12-deficient cancer cells showed reduced tumorigenicity, suggesting an immune evasion by cancer cell-derived Myl9/12. On the other hand, CD69-deficient mice showed increased frequency of cytotoxic differentiated CD8T cells in the tumor microenvironment. Thus, the CD69-Myl9/12 system promotes cancer immune evasion by controlling differentiation of intratumoral CD8T cells.

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまでに抗腫瘍免疫応答への関与が着目されていなかったCD69-Myl9/12システムに焦点を当てている。Myl9/12は我々が独自に見出したCD69の機能的リガンドであり、国内外を通じて類似の研究はなく、独自の独創的な研究である。さらに、Myl9/12の放出はがん細胞自体に依存していると考えられるため、抗Myl9/12抗体投与は腫瘍組織を選択的に標的とする、副作用の少ない治療法になる可能性がある。今後、我々の知見からCD69-Myl9/12システムを標的とした新規がん免疫療法が開発され、がん治療に新しい局面が拓かれることを期待している。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2020 2019 2018 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (9 results) Remarks (2 results)

  • [Journal Article] CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy2020

    • Author(s)
      Hara Ayaka、Koyama-Nasu Ryo、Takami Mariko、Toyoda Takahide、Aoki Takahiro、Ihara Fumie、Kobayashi Masayoshi、Hirono Seiichiro、Matsutani Tomoo、Nakayama Toshinori、Iwadate Yasuo、Motohashi Shinichiro
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: - Issue: 5 Pages: 1239-1254

    • DOI

      10.1007/s00262-020-02742-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Essential Role for CD30-Transglutaminase 2 Axis in Memory Th1 and Th17 Cell Generation2020

    • Author(s)
      Suzuki Akane S.、Yagi Ryoji、Kimura Motoko Y.、Iwamura Chiaki、Shinoda Kenta、Onodera Atsushi、Hirahara Kiyoshi、Tumes Damon J.、Koyama-Nasu Ryo、Iismaa Siiri E.、Graham Robert M.、Motohashi Shinichiro、Nakayama Toshinori
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 1536-1536

    • DOI

      10.3389/fimmu.2020.01536

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d‐independent manner2020

    • Author(s)
      Aoki Takahiro、Takami Mariko、Takatani Tomozumi、Motoyoshi Kiwamu、Ishii Ayana、Hara Ayaka、Toyoda Takahide、Okada Reona、Hino Moeko、Koyama‐Nasu Ryo、Kiuchi Masahiro、Hirahara Kiyoshi、Kimura Motoko Y.、Nakayama Toshinori、Shimojo Naoki、Motohashi Shinichiro
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 7 Pages: 2223-2233

    • DOI

      10.1111/cas.14428

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new therapeutic target: the CD69-Myl9 system in immune responses2019

    • Author(s)
      Kimura Motoko Y.、Koyama-Nasu Ryo、Yagi Ryoji、Nakayama Toshinori
    • Journal Title

      Seminars in Immunopathology

      Volume: - Issue: 3 Pages: 349-358

    • DOI

      10.1007/s00281-019-00734-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ACC1 determines memory potential of individual CD4+ T cells by regulating de novo fatty acid biosynthesis2019

    • Author(s)
      Yusuke Endo, Atsushi Onodera, Kazushige Obata-Ninomiya, Ryo Koyama-Nasu, Hikari K. Asou, Toshihiro Ito, Takeshi Yamamoto, Toshio Kanno, Takahiro Nakajima, Kenji Ishiwata, Hirotaka Kanuka, Damon J. Tumes, Toshinori Nakayama
    • Journal Title

      Nature Metabolism

      Volume: 1(2) Issue: 2 Pages: 261-275

    • DOI

      10.1038/s42255-018-0025-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity2018

    • Author(s)
      Funato K, Hayashi T, Echizen K, Negishi L, Shimizu N, Koyama-Nasu R, Nasu-Nishimura Y, Morishita Y, Tabar V, Todo T, Ino Y, Mukasa A, Saito N & Akiyama T.
    • Journal Title

      EMBO Reports

      Volume: 19 Issue: 11 Pages: 45587-45587

    • DOI

      10.15252/embr.201745587

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crucial role of CD69 in anti-tumor immunity through regulating the exhaustion of tumor-infiltrating T cells2018

    • Author(s)
      Mita Y, Kimura MY, Hayashizaki K, Koyama-Nasu R, Ito T, Motohashi S, Okamoto Y & Nakayama T
    • Journal Title

      International Immunology

      Volume: 30 Issue: 12 Pages: 559-567

    • DOI

      10.1093/intimm/dxy050

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] CD1d expression in glioblastoma is a promising target for NKT cell- based cancer immunotherapy2019

    • Author(s)
      Hara, A., Nasu, R., Takami, M., Hirono, S., Matsutani, T., Nakayama, T., Iwadate, Y., Motohashi, S.
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] CD1d expression in glioblastoma is a promising target for NKT cell- based cancer immunotherapy2019

    • Author(s)
      Hara, A., Nasu, R., Takami, M., Hirono, S., Matsutani, T., Nakayama, T., Iwadate, Y., Motohashi, S.
    • Organizer
      EMBO workshop CD1-MR1
    • Related Report
      2019 Research-status Report
  • [Presentation] がん免疫療法の新たなターゲットとしてのCD69の可能性2019

    • Author(s)
      木村元子、那須亮、三田恭義、中山俊憲
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Inhibition of acetyl-CoA carboxylase enhances memory Th2 cell generation and Th2 mediated anti-tumor immunity2019

    • Author(s)
      那須亮、遠藤祐介、伊藤俊広、木村元子、中山俊憲
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 膠芽腫に発現するCD1d分子はNKT細胞を用いた免疫療法における有望な標的となる2019

    • Author(s)
      原 彩佳、那須 亮、高見 真理子、廣野 誠一郎、松谷 智郎,、中山 俊憲,、岩立 康男、本橋 新一郎
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Crucial role for CD69 in anti-tumor immunity2018

    • Author(s)
      Mita Y, Kimura M, Nasu R, Motohashi S, Okamoto Y & Nakayama T
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] nti-tumor immunity via the superoxide-eosinophil axis induced by lipophilic component of Mycobacterium lipomannan2018

    • Author(s)
      Ito T, Hirahara K, Nasu R, Yano I, Motohashi S & Nakayama T
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] CD69による抗腫瘍免疫制御2018

    • Author(s)
      三田 恭義, 木村 元子, 那須 亮, 本橋新一郎, 岡本 美孝, 中山 俊憲
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 好酸球およびエフェクター記憶 Th2 細胞の活性化によるMycobacterium lipomannanの抗腫瘍免疫2018

    • Author(s)
      伊藤 俊広, 平原 潔, 那須 亮, 小野寺 淳, 矢野 郁也, 本橋新一郎, 中山 俊憲
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 千葉大学大学院医学研究院 免疫発生学HP

    • URL

      https://www.m.chiba-u.ac.jp/class/meneki/jisseki/index.html

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Remarks] 千葉大学大学院医学研究院免疫発生学

    • URL

      https://www.m.chiba-u.ac.jp/class/meneki/

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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