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The role of lipid mediator in the tumor immune microenvironment of breast cancer and its therapeutic application

Research Project

Project/Area Number 19H03714
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionHyogo Medical University (2021)
Niigata University (2019-2020)

Principal Investigator

Nagahashi Masayuki  兵庫医科大学, 医学部, 准教授 (30743918)

Co-Investigator(Kenkyū-buntansha) 奥田 修二郎  新潟大学, 医歯学系, 教授 (00512310)
阿部 学  新潟大学, 脳研究所, 准教授 (10334674)
諸 和樹  新潟大学, 医歯学総合病院, 特任助教 (10745566)
崎村 建司  新潟大学, 脳研究所, フェロー (40162325)
三好 康雄  兵庫医科大学, 医学部, 教授 (50283784)
若井 俊文  新潟大学, 医歯学系, 教授 (50372470)
土田 純子  新潟大学, 医歯学総合研究科, 客員研究員 (90769415)
五十嵐 道弘  新潟大学, 医歯学系, 教授 (50193173)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2020: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2019: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords脂質メディエーター / スフィンゴシン-1-リン酸 / 乳癌 / 腫瘍免疫微小環境 / スフィンゴシン-1-リン酸 / 治療 / スフィンゴシン‐1-リン酸
Outline of Research at the Start

近年、腫瘍免疫の重要性が明らかとなり、「微小環境において如何に腫瘍免疫を制御し、ミクロ病変を根絶できるか」が癌の転移・再発抑制の1つの鍵と考えられる。申請者は「乳癌患者の腫瘍免疫微小環境において脂質メディエーター・スフィンゴシン-1-リン酸(S1P)が重要な役割を担っている」と仮説を立て、本研究を企画した。本研究の目的は、腫瘍免疫微小環境におけるS1Pの役割を解明し、その臨床的意義を明らかにして治療応用を目指すことである。本研究では、動物実験及び患者検体の解析により腫瘍免疫微小環境における脂質分子の働きを解明し、脂質分子を標的とし腫瘍免疫微小環境を制御する新たな治療開発のための研究基盤を築く。

Outline of Final Research Achievements

We hypothesized that a lipid mediator, sphingosine-1-phosphate (S1P), plays an important role in the tumor immune microenvironment of breast cancer patients, and planned this study. The aim of this study is to elucidate the role of S1P in the tumor immune microenvironment, clarify its clinical significance, and establish a research base for its therapeutic application. Animal studies showed that cancer development is difficult in tumor microenvironments to which S1P is not supplied, suggesting that the importance of S1P in tumor microenvironments. Immunohistochemistry of surgical specimens and bioinformatics analysis of transcriptome data revealed that S1P is associated with antitumor immunity and escape mechanisms of the immune system in the tumor microenvironment.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、蛋白ではなく脂質分子であるS1Pの腫瘍免疫微小環境における働きを解析し、癌と宿主とが産生するS1Pが腫瘍形成において必須の役割を担っていることと、腫瘍免疫微小環境において、抗腫瘍免疫と免疫逃避機構とに関連していることを明らかにしたことである。社会的意義として、本研究の成果を基盤として、今後、免疫療法をはじめとした乳癌の新しい治療法開発につながり、ひいては乳癌治療成績の向上につながっていくことが期待されることである。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (10 results)

All 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] Roswell Park Cancer Institute/Virginia Commonwealth University(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ロズウェルパーク癌研究所(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] バージニア州立大学/ロズウェルパーク癌研究所(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Plasma Sphingosine-1-Phosphate Levels Are Associated with Progression of Estrogen Receptor-Positive Breast Cancer2021

    • Author(s)
      Ikarashi Mayuko、Tsuchida Junko、Nagahashi Masayuki、Takeuchi Shiho、Moro Kazuki、Toshikawa Chie、Abe Shun、Ichikawa Hiroshi、Shimada Yoshifumi、Sakata Jun、Koyama Yu、Sato Nobuaki、Hait Nitai C.、Ling Yiwei、Okuda Shujiro、Takabe Kazuaki、Wakai Toshifumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 24 Pages: 13367-13367

    • DOI

      10.3390/ijms222413367

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Low intratumoral genetic neutrophil-to-lymphocyte ratio (NLR) is associated with favorable tumor immune microenvironment and with survival in triple negative breast cancer (TNBC)2021

    • Author(s)
      Tokumaru Y, Oshi M, Patel A, Katsuta E, Yan L, Angarita FA, Dasgupta S, Nagahashi M, Matsuhashi N, Futamura M, Yoshida K, Takabe K.
    • Journal Title

      Am J Cancer Res

      Volume: 11 Pages: 3320-3334

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sphingosine Kinase 1 is Associated With Immune Cell Related Gene Expressions in Human Breast Cancer2020

    • Author(s)
      Junko Tsuchida, Masayuki Nagahashi, Masato Nakajima, Eriko Katsuta, Omar M. Rashid, Qianya Qi, Li Yan, Shujiro Okuda, Kazuaki Takabe, Toshifumi Wakai
    • Journal Title

      Journal of Surgical Research

      Volume: 15 Pages: 645-656

    • DOI

      10.1016/j.jss.2020.06.057

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intra-tumoral angiogenesis is associated with inflammation, immune reaction and metastatic recurrence in breast cancer2020

    • Author(s)
      Oshi M, Newman S, Tokumaru Y, Yan L, Matsuyama R, Endo I, Nagahashi M, Takabe K
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 18 Pages: 6708-6708

    • DOI

      10.3390/ijms21186708

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 肥満状態下の乳癌転移におけるスフィンゴシン-1-リン酸の役割2021

    • Author(s)
      永橋 昌幸,土田 純子,諸 和樹,長谷川 遙,小幡 泰生,遠藤 麻巳子, 利川 千絵,五十嵐 麻由子,小山 諭,高部 和明,若井 俊文
    • Organizer
      第29回日本乳癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 慢性炎症による癌の増殖・転移を促進する脂質メディエーター分子機構2020

    • Author(s)
      永橋 昌幸,土田 純子,油座 築,諸 和樹,根本 万里子,廣瀬 雄己,利川 千絵,五十嵐 麻由子,三浦 宏平,市川 寛,羽入 隆晃,滝沢 一泰,中島 真人,島田 能史,小林 隆,坂田 純,石川 卓,亀山 仁史,若井 俊文
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Involvement of sphingosine-1-phosphate in tumor immune microenvironment of breast cancer patients2020

    • Author(s)
      Junko Tsuchida, Masayuki Nagahashi, Mayuko Ikarashi, Kazuki Moro, Chie Toshikawa, Hiroshi Ichikawa, Yoshifumi Shimada, Kazuaki Takabe, Toshifumi Wakai
    • Organizer
      The 15th Annual Academic Surgical Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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