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Identification of the secondary mechanism for immune evasion in cancer at the immune checkpoint inhibition

Research Project

Project/Area Number 17K07171
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionKyushu University

Principal Investigator

Kanae Yumimoto  九州大学, 生体防御医学研究所, 特別研究員 (30596838)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords免疫チェックポイント
Outline of Final Research Achievements

We tried to compare between "susceptible" and "resistant" cancers for the inhibition of PD-1/PD-L1 pathway, and attempted to describe a second immune checkpoint avoidance pathway by elucidating the differences. We found that we can uses B16F1 and B16F10 melanoma cells as a model of "susceptible" and "resistant" cancers for the inhibition of PD-1/PD-L1 pathway when transplanted via spleen. Mutagenesis and RNAseq analysis were performed after mutagenesis of PD-L1-deficient B16F1 cells, which were transformed to the PD-1/PD-L1 pathway "resistant cancer". By comparing the results from mouse with those of human immune checkpoint-sensitive and resistant patients, a total of 24 molecules were deduced as candidate master factors for the second avoidance mechanism from cancer immunity.

Academic Significance and Societal Importance of the Research Achievements

近年、免疫チェックポイント阻害剤の明確な治療効果が示され、国内でも悪性黒色腫や非小細胞肺がんで承認されるなど、ますます注目を集めている。しかし、多くのがんにおいて奏効率は10%~30%程度であり、さらなる向上が求められている。同時に、抗体医薬を用いた治療はその高額な薬価が社会問題になっており、治療が有効な患者を選択するためのバイオマーカーの発見が必要とされている。本研究は、併用療法の最適化および新規バイオマーカー発見といった免疫チェックポイント阻害療法の拡充プロセスへ必須であると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Book (2 results)

  • [Journal Article] Recent insight into the role of FBXW7 as a tumor suppressor2020

    • Author(s)
      Yumimoto Kanae、Nakayama Keiichi I.
    • Journal Title

      Seminars in Cancer Biology

      Volume: 未定 Pages: 1-15

    • DOI

      10.1016/j.semcancer.2020.02.017

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potentials of C-C Motif Chemokine 2-C-C Chemokine Receptor Type 2 Blockers Including Propagermanium as Anticancer Agents2019

    • Author(s)
      Yumimoto Kanae、Sugiyama Shigeaki、Mimori Koshi、Nakayama Keiichi I.
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 7 Pages: 2090-2099

    • DOI

      10.1111/cas.14075

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SCFFbxw7 ubiquitylates KLF7 for degradation in a manner dependent on GSK-3-mediated phosphorylation.2019

    • Author(s)
      Sugiyama S, Yumimoto K, Inoue I, Nakayama KI
    • Journal Title

      GENE CELLS

      Volume: 印刷中 Issue: 5 Pages: 354-365

    • DOI

      10.1111/gtc.12680

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Degradation of the endoplasmic reticulum-anchored transcription factor MyRF by the ubiquitin ligase SCFFbxw7 in a manner dependent on the kinase GSK-3.2018

    • Author(s)
      Nakayama S, Yumimoto K, Kawamura A, Nakayama KI.
    • Journal Title

      J. Biol. Chem.

      Volume: 293(15) Issue: 15 Pages: 5705-5714

    • DOI

      10.1074/jbc.ra117.000741

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] がん細胞が抗PD-1/PD-L1免疫治療を免れるための分子経路の探索2019

    • Author(s)
      弓本 佳苗、中山 敬一
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] がん細胞が免疫チェックポイント阻害を免れる分子経路のゲノムワイドスクリーニング2018

    • Author(s)
      弓本 佳苗、中山 敬一
    • Organizer
      日本分子生物学会
    • Related Report
      2018 Research-status Report
  • [Book] ユビキチン・プロテアソーム系 (UPS) とがん治療戦略2018

    • Author(s)
      弓本 佳苗、中山 敬一
    • Total Pages
      7
    • Publisher
      羊土社
    • ISBN
      4758103739
    • Related Report
      2018 Research-status Report
  • [Book] がん転移学(上)がんの浸潤と転移のメカニズム2017

    • Author(s)
      杉山 成明、弓本 佳苗、中山 敬一
    • Total Pages
      305
    • Publisher
      日本臨牀社
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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