Roles for senescence factors of the cellular metabolism in the anti-cancer T-cell immunity

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20670
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0702:Biology at cellular to organismal levels, and related fields
• Research Institution: Kyoto University (2022-2023); Foundation for Biomedical Research and Innovation at Kobe (2021)
• Principal Investigator: Mori Mayumi 京都大学, 医学研究科, 特定講師 (70710060)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: 老化 / がん免疫 / 代謝

Outline of Final Research Achievements

Aging will alter the physiological functions all over the body including the immune system. One of such changes in so-called "immune-aging" is that the thymic involution eventually ends up with dysregulation of T cell immunity. However, it is not clear what causes T cell immune-aging and how it happens. This research project analyzed the effects of various reagents that interfere with cellular metabolism on T cell immune responses such as cancer cell eradication. As an instance, calcitriol (active-form vitamin D) was found to surpress the proliferation of activated CD8 T cells but also to reduce the expression of a senescence marker PD1 at the same time, and to maintain the immune responses against cancer cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会において、加齢・老化にともなう身体機能の低下を防ぎ、健康長寿を目指すことが喫緊の課題である。その中でも T 細胞はその産生臓器である胸腺が年齢とともに不可逆的に退縮し、免疫老化によって癌や感染症に対する抵抗性の低下や、自己免疫疾患を招く大きな要因となる。本研究によって、一つでも T 細胞の免疫老化に対して直接作用しうる薬剤・化合物が見出されたことは、今後の抗老化医療技術や医薬品開発の一助となる。また、学術的にも免疫老化において細胞レベルの代謝変化から老化・抗老化または癌免疫応答に関与する因子は重要な発見であり、今後も派生的・発展的な研究継続が見込まれる。