Analyses on the role of Eomesodermin in CD8+ T cell exhaustion

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07715
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kitasato University
• Principal Investigator: Eshima Koji 北里大学, 医学部, 准教授 (30327324)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: T細胞疲弊化 / Eomesodermin / トランスジェニックマウス / 転写因子

Outline of Final Research Achievements

Although in treating cancers, T cell exhaustion often emerges as one of the problems to be overcome, the detailed mechanisms of induction of T cell exhaustion still remain largely unclear. In this study, to investigate the possible involvement of Eomesodermin (Eomes), a transcriptional regulator found in exhausted T cells, we generated and analyzed the transgenic mice where Eomes is constitutively expressed in T cells. The results suggested that in Eomes-Tg, T cells expressed some of exhaustion markers and their responsiveness was attenuated, indicating that Eomes may indeed contribute to induce T cell exhaustion. The results also suggested that Eomes may regulate the expression of exhaustion markers either by enhancing the effect of antigen stimulation or by acting independently of TCR stimulation. Furthermore, it was also suggested that Eomes may elicit T cell exhaustion by inducing miR-31, which were recently shown to be an important accelerator of T cell exhaustion.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

抗腫瘍免疫療法において「免疫チェックポイント阻害」が非常に有効であることは，抗腫瘍療法において腫瘍特異的なT細胞の疲弊化からの回復が重要であることを示している。しかし，T細胞疲弊化の機序の詳細について未だ不明の部分が多く，PD-1やCTLA-4に対する抗体などを用いた既存の治療法以外，このような観点からの新たな治療法開発はあまり進んでいない。本研究において疲弊化T細胞内に高発現する転写因子EomesがT細胞疲弊化に寄与していることが示唆され，Eomesが疲弊化解除のための標的分子となりうる可能性が示唆された。