Foxp3 expression in adult T-cell leukemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09925
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto 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
• Keywords: 成人T細胞白血病 / FOXP3 / 制御性T細胞 / CD58

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.

Free Research Field

血液内科学

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。