Spatiotemporal T-cell differentiation dynamics in the tumor "peripheral" environment

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19459
• 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: Okayama University
• Principal Investigator: Togashi Yosuke 岡山大学, 医歯薬学域, 教授 (80758326)
• Co-Investigator(Kenkyū-buntansha): 宝田 剛志 岡山大学, 医歯薬学域, 教授 (30377428)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 腫瘍免疫 / ミトコンドリア

Outline of Final Research Achievements

In previous studies, we found that anti-senescence molecules and mitochondria in the tumor "peripheral" environment could be related to antitumor immunity. In this study, we introduced the identified genes into T cells, clearly showing increased activation. In addition, T cells with mitochondrial abnormalities were senescent with metabolic abnormalities and impaired activation and memory formation. We attempted spatial gene regulation in immune cells using our original TRE-PA-Cre system, but many immune cells died after blue light irradiation, making it difficult to use this systme. In contrast, T cell-specific conditional knockout mice showed reduced anti-tumor immune response including durable response, suggesting the importance of these factors.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

抗腫瘍免疫応答では腫瘍局所の免疫応答ばかりが注目されてきたが、本研究成果は周辺の環境も重要であることを証明することができた。特に同定した遺伝子やミトコドリア機能に関しては、がん免疫療法の新たなバイオマーカーや、細胞療法などに応用できる可能性がある。また手術による切除範囲に関しても一石を投じることができるような成果である。マウスの樹立は今回は難しかったが、今後も時空間的制御に利用できるような系の構築を目指していきたい。