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Nutritional approach for activation of tumor immunity: mechanisms and therapeutic applications

Research Project

Project/Area Number 21K19748
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionMiyagi Prefectural Hospital Organization Miyagi Cancer Center

Principal Investigator

Ito Shigemi  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (80600006)

Co-Investigator(Kenkyū-buntansha) 田沼 延公  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 部長 (40333645)
Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords腫瘍免疫 / ビタミン / ナイアシン / 食事 / 栄養 / がん / 食事療法
Outline of Research at the Start

近年のがん免疫療法の発展は目覚ましいが、耐性症例の多さなど、課題も多い。申請者らは最近、別目的にて試行中の食事介入(あるビタミンの摂取制限)に「腫瘍免疫を賦活する作用」があることを、思いがけず発見した。本研究では、独自の代謝遺伝子改変マウスの解析等を中心に、その分子メカニズムを解明し、栄養学的アプローチによって腫瘍免疫に介入する途を探る。栄養学的観点から、新たながんイムノセラピー開発の基礎となるデータを収集する。

Outline of Final Research Achievements

Recently, much attention has been paid to the crosstalk between diet and tumor immunity. The aim of this study was to elucidate the mechanism where the restriction of dietary niacin upregulates tumor immunity. By modifying diet and genetically engineered models in mice, we found that dietary nicotinic acid is converted to nicotinic acid riboside, which circulates in the blood. Niacin restriction markedly reduced blood nicotinic acid riboside concentrations. On the other hand, niacin restriction also resulted in rapid changes in the gut microbiota. These findings suggest that niacin restriction stimulates tumor immunity via either or both of these two mechanisms.

Academic Significance and Societal Importance of the Research Achievements

近年のがん免疫療法の発展は目覚ましいが、耐性症例の多さなど、課題も多い。その一部は、例えば腫瘍ごとに異なる腫瘍ネオ抗原の多寡などで説明されるようになったが、未だ不明の点が多い。本研究では、食事が腫瘍免疫の活性に影響し得ることを実験的に示した。さらにその作用メカニズムの一端として、血中栄養素レベルの変動と腸内細菌叢の変化を同定した。さらなるメカニズム解明や、新規イムノセラピーへの発展が期待される。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (7 results)

All 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (4 results) (of which Invited: 2 results)

  • [Journal Article] A case of anaplastic pancreatic cancer with osteoclast-like giant cells during follow-up of a branch-duct pancreatic intraductal papillary mucinous tumor2022

    • Author(s)
      太田 健介、佐藤 郁郎、虻江 誠、目黒 陸、日下 順、岩井 渉、涌井 裕太、及川 智之、鈴木 眞一、伊藤 しげみ
    • Journal Title

      Nippon Shokakibyo Gakkai Zasshi

      Volume: 119 Issue: 10 Pages: 961-968

    • DOI

      10.11405/nisshoshi.119.961

    • ISSN
      0446-6586, 1349-7693
    • Year and Date
      2022-10-10
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PP6 deficiency in mice with KRAS mutation and Trp53 loss promotes early death by PDAC with cachexia-like features.2022

    • Author(s)
      Fukui K, Nomura M, Kishimoto K, Tanuma N, Kurosawa K, Kanazawa K, Kato H, Sato T, Miura S, Miura K, Sato I, Tsuji H, Yamashita Y, Tamai K, Watanabe T, Yasuda J, Tanaka T, Satoh K, Furukawa T, Jingu K, Shima H.
    • Journal Title

      Cancer Sci.

      Volume: 印刷中 Issue: 5 Pages: 1613-1624

    • DOI

      10.1111/cas.15315

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ppp6c deficiency accelerates K-rasG12D -induced tongue carcinogenesis.2021

    • Author(s)
      Kishimoto K, Kanazawa K, Nomura M, Tanaka T, Shigemoto-Kuroda T, Fukui K, Miura K, Kurosawa K, Kawai M, Kato H, Terasaki K, Sakamoto Y, Yamashita Y, Sato I, Tanuma N, Tamai K, Kitabayashi I, Matsuura K, Watanabe T, Yasuda J, Tsuji H, Shima H.
    • Journal Title

      Cancer Med.

      Volume: 10(13) Issue: 13 Pages: 4451-4464

    • DOI

      10.1002/cam4.3962

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] NAD biogenesis is a targetable vulnerability of small-cell lung and prostate cancers2022

    • Author(s)
      大内麻衣、宮原周子、野村美有樹、坂本良美、伊藤しげみ、盛田麻美、佐藤卓、菊池直彦、田沼延公
    • Organizer
      第95回 日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Systemic niacin metabolism that limits efficacy of NAD-targeted therapy in cancer2022

    • Author(s)
      野村美有樹、大内麻衣、伊藤しげみ、盛田麻美、菊池直彦、佐藤卓、 中川崇、田沼延公
    • Organizer
      第95回 日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Targeting NAD metabolism in cancer.2021

    • Author(s)
      Tanuma N
    • Organizer
      第80回日本癌学会学術集会 JCA-AACR Joint Symposia “Cancer Metabolism”(横浜)
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Metabolism-targeting therapy and precision nutrition in cancer2021

    • Author(s)
      Tanuma N
    • Organizer
      第80回日本癌学会学術集会 モーニングレクチャー(横浜)
    • Related Report
      2021 Research-status Report
    • Invited

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Published: 2021-07-13   Modified: 2024-01-30  

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