2023 Fiscal Year Final Research Report
Elucidation of the role for transcription factor JunB in exhausted CD8 + T cells
| Project/Area Number |
22K15500
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 49070:Immunology-related
|
|---|
| Research Institution | Okinawa Institute of Science and Technology Graduate University |
|---|
Principal Investigator |
Taira Naoyuki 沖縄科学技術大学院大学, 統合オープンシステムユニット, ポストドクトラルスカラー (40813621)
|
|---|
| Project Period (FY) |
2022-04-01 – 2024-03-31
|
| Keywords | JunB / Exhausted CD8+ T cells / Tpex / Tex |
|---|
| Outline of Final Research Achievements |
Exhaustion of CD8+ T cells is a critical issue in cancer immunotherapy. We have found that JunB is essential for effector cell survival, but its function in exhaustion is not known. Therefore, we focused our study on exhaustion and JunB. JunB expression on effector CD8+ T cells during tumor invasion was higher than on effector CD8+ T cells in the acute infection model. CD8+ T cells in the pre-activated state in the lymph nodes surrounding the tumor expressed little JunB but expressed high levels of JunB when infiltrating the tumor. Effector CD8+ T cells in the tumor tissue consisted of progenitor exhausted cells and terminal exhausted cells, and decreased JunB expression in progenitor exhausted cells resulted in their differentiation into terminal exhausted cells. This suggests that maintenance of JunB expression is important in progenitor cells.
|
| Free Research Field |
免疫学
|
| Academic Significance and Societal Importance of the Research Achievements |
近年がんの三大療法に次ぐ治療として免疫療法に注目が集まっている。しかしながら、免疫療法において解決すべき課題としてエフェクター機能の低下を伴うT細胞の疲弊化が知られている。この疲弊化を防ぐため精力的に世界中で研究が行われているが、未だ決定的な解決方法は見つかっていない。本研究で着目したJunBはエフェクター細胞の生存に関わるだけでなく、疲弊化を抑制する可能性が見出された。この研究結果を元にさらなる詳細なメカニズムが判明すれば、この疲弊化を制御するようなメカニズムが明らかになると考えている。その結果、がんの免疫療法のさらなる進展が期待でき、がんで苦しむ人々を救う治療法の確立に貢献できるだろう。
|
