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Foxp3 expression in adult T-cell leukemia

Research Project

Project/Area Number 17K09925
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKyoto University

Principal Investigator

Hishizawa Masakatsu  京都大学, 医学研究科, 助教 (90444455)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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成人T細胞白血病 / FOXP3 / 制御性T細胞 / CD58 / 免疫不全 / Foxp3 / 血液内科学
Outline of Final Research Achievements

ATL cells usually express forkhead box P3 (FOXP3). However, the mechanisms of FOXP3 expression remain unclear. Analysis of DNA methylation in ATL showed a part of patients hypomethylated the TSDR. Flowcytometric analysis showed CD3+CD4+TSLC-1+CD7- cells were mainly HTLV-1-infected cells and possess the regulatory T cell (Treg) phenotype, such as FOXP3, CCR4. Loss of CD58 is a common mechanism for tumor immune evasion in lymphoid malignancies. Epigenetic library screening demonstrated that EZH2 inhibitors enhanced CD58 expression. EZH2 inhibitor enhanced interferon-γ production of T and NK cells against lymphoma cells. These results indicated that downregulation of CD58 could be a mechanism for tumor immune escape and provide a molecular basis for immunotherapy.

Academic Significance and Societal Importance of the Research Achievements

FOXP3やCD58といった免疫逃避機構に関わる分子の発現や抑制が、epigeneticな機序でされており、ATLにおける免疫不全や発症に関わる可能性があり、さらに、今後治療標的としても候補となりうる。

Report

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

    (1 results)

All 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] EZH2 inhibitors restore epigenetically silenced CD58 expression in B cell lymphomas2020

    • Author(s)
      Yasuyuki Otsuka, Momoko Nishikori, Hiroshi Arima, Kiyotaka Izumi, Toshio Kitawaki, Masakatsu Hishizawa Akifumi Takaori-Kondo
    • Journal Title

      Molecular Immunology

      Volume: 119 Pages: 35-45

    • DOI

      10.1016/j.molimm.2020.01.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

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

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