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Resistant mechanisms and models by evading anti-leukemia immunity

Research Project

Project/Area Number 17K09953
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionNational Cancer Center Japan

Principal Investigator

Minami Yosuke  国立研究開発法人国立がん研究センター, 東病院, 科長 (60513752)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords白血病 / 分子標的療法 / 抗腫瘍免疫 / PD-1抗体 / 制御性T細胞 / 急性骨髄性白血病 / PD-1 / 免疫制御 / 耐性
Outline of Final Research Achievements

Using cells derived from patients with Acute Myeloid Leukemia; AML, we examined Treg cells and immune effects on leukemia by FCM and NGS assays.
Tumor cells use immune-checkpoint pathways to evade the host immune system and suppress immune cell function. These cells express programmed cell-death protein 1 ligand 1 (PD-L1)/PD-L2, which bind to the programmed cell-death protein 1 (PD-1) present on cytotoxic T cells, trigger inhibitory signaling, and reduce cytotoxicity and T-cell exhaustion. Immune-checkpoint blockade can inhibit this signal and may serve as an effective therapeutic strategy in patients with solid tumors. Several trials have been conducted on immune-checkpoint inhibitor therapy in patients with leukemia. We examine the biomarker during PD-1 antibody therapy.

Academic Significance and Societal Importance of the Research Achievements

急性骨髄性白血病(Acute Myeloid Leukemia; AML)において、再発率の高さが臨床上の問題点であり、治療後の残存と耐性機序の解明が求められている。
PD-1抗体(ニボルマブ)の新たな効果/抵抗性のマーカーについて明らかにすることは、新たな治療法の進歩につながる。

Report

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

    (8 results)

All 2019 2018

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results)

  • [Journal Article] Efficacy of Hedgehog inhibitors in acute myeloid leukemia and establishment of valid biomarkers2019

    • Author(s)
      南 陽介
    • Journal Title

      Rinsho Ketsueki

      Volume: 60 Issue: 7 Pages: 843-846

    • DOI

      10.11406/rinketsu.60.843

    • NAID

      130007687995

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Targeting Hedgehog (Hh) Pathway for the Acute Myeloid Leukemia Treatment2019

    • Author(s)
      Terao Toshiki、Minami Yosuke
    • Journal Title

      Cells

      Volume: 8 Issue: 4 Pages: 312-312

    • DOI

      10.3390/cells8040312

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure2019

    • Author(s)
      Hughes Timothy P.、Minami Yosuke、Yeung David、Ross David M.、Tallman Martin S.、Park Jae H.、Druker Brian J.、Hynds David、Duan Yuyan、Meille Christophe、Hourcade-Potelleret Florence、Vanasse K. Gary、Lang Fabian、Kim Dong-Wook, et al.
    • Journal Title

      New England Journal of Medicine

      Volume: 381 Issue: 24 Pages: 2315-2326

    • DOI

      10.1056/nejmoa1902328

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Precision medicine and novel molecular target therapies in acute myeloid leukemia: the background of hematologic malignancies (HM)-SCREEN-Japan 012019

    • Author(s)
      Miyamoto Kenichi、Minami Yosuke
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 24 Issue: 8 Pages: 893-898

    • DOI

      10.1007/s10147-019-01467-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potent antiproliferative effect of fatty‐acid derivative AIC‐47 on leukemic mice harboring BCR‐ABL mutation2019

    • Author(s)
      Shinohara H, Sugito N, Kuranaga Y, Heishima K, Minami Y, Naoe T, Akao Y.
    • Journal Title

      Cancer Sci.

      Volume: 110 Issue: 2 Pages: 751-760

    • DOI

      10.1111/cas.13913

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Guest editorial: chronic myeloid leukemia2018

    • Author(s)
      Minami Yosuke
    • Journal Title

      International Journal of Hematology

      Volume: 108 Issue: 4 Pages: 353-354

    • DOI

      10.1007/s12185-018-2521-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chronic myeloid leukemia stem cells and molecular target therapies for overcoming resistance and disease persistence2018

    • Author(s)
      Inoue Ai、Kobayashi Chiharu I.、Shinohara Haruka、Miyamoto Kenichi、Yamauchi Nobuhiko、Yuda Junichiro、Akao Yukihiro、Minami Yosuke
    • Journal Title

      International Journal of Hematology

      Volume: 108 Issue: 4 Pages: 365-370

    • DOI

      10.1007/s12185-018-2519-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment2018

    • Author(s)
      Okada M, Imagawa J, et al.
    • Journal Title

      Clin Lymphoma Myeloma Leuk.

      Volume: 18 Issue: 5 Pages: 353-360

    • DOI

      10.1016/j.clml.2018.03.004

    • NAID

      120006463738

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access

URL: 

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

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