Development of a novel therapeutic approach for refractory tumors that improves the T-cell activation threshold through metabolic modulation

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19461
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Muraoka Daisuke 愛知県がんセンター(研究所), 腫瘍免疫制御TR分野, ユニット長 (20608955)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 代謝 / 抗原提示 / キラーT細胞

Outline of Final Research Achievements

It has been reported that intracellular metabolism is involved in the activation and differentiation of T cells, and that the enhancement of glycolysis after antigen stimulation is essential for T cell activation. However, the key mechanisms that trigger this glycolytic enhancement following antigen stimulation remain unclear. We have demonstrated that even under weak antigen stimulation, stimulating mitochondria with our compounds can enhance glycolysis and lead to T cell activation. In this research proposal, we aimed to investigate the involvement of signaling molecules in the enhancement of the glycolytic pathway induced by activation of the compound's electron transfer system. As a result, our findings suggest the potential involvement of cell-cell interactions in the metabolic changes observed in T cells.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

T細胞の活性化には抗原刺激後の解糖系の亢進が必須です。しかし、抗原刺激後の解糖系亢進を惹起する機構については完全には明らかにされていません。そこで、我々は、弱い抗原刺激を受けたT細胞においてミトコンドリアを刺激して解糖系を亢進する化合物を用いてこれを明らかにすることを目指しました。その結果、化合物を用いるとT細胞の細胞間相互作用に関する分子に変化があることがわかりました。細胞の代謝と細胞間相互作用に関する報告は少なく、今後の展開が期待されます。