Foxp3 expression in adult T-cell leukemia
| 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 |
|
|---|
| 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)
Research Products
(1 results)
