Foundation for Vgamma9Vdelta2 T cell anti-tumor immunotherapy targeting tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18123
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Shimizu Teruki 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (90530361)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: γδT細胞 / Vγ9Vδ2T細胞 / 癌微小環境 / 膀胱癌 / 免疫疲弊 / Tim-3

Outline of Final Research Achievements

In this project, the blood samples suffering from urinary bladder cancer were collected, cultured and tested for efficiency of Vγ9Vδ2 T cell expansion and quality of cancer cell-killing ability. Of immune exhaustion markers examined, Tim-3 molecule was identified which was highly expressed on Vγ9Vδ2 T during culture period. We proposed that manipulating the tumor microenvironment to reduce the expression of exhaustion marker ”Tim-3” was essential to improve cancer outcomes. By blocking Tim-3 pathway, we showed the potential for targeting Tim-3 to assist in enhancing an Vγ9Vδ2 T anti-tumor immune response in in vitro experiment in TCCSUP bladder cancer cell line using flow cytometry. We will continue to work on the essential role of Tim-3 molecule, which may be a promising therapeutic target to improve Vγ9Vδ2 T cell-based adoptive immunotherapy for urinary bladder cancer in in vivo mouse model experiment as well as in vitro experiment.

Free Research Field

γδT細胞、癌免疫細胞療法

Academic Significance and Societal Importance of the Research Achievements

膀胱癌担癌患者の培養実施および抗腫瘍効果を実施し、結果、良好な培養効率を確認できたためγδT細胞免疫療の臨床応用に向けた予備検討を行う事ができた。細胞療法の際に投与したγδT細胞の癌微小環境下での免疫疲弊に関与する細胞分子メカニズムに着目した検討を実施した。癌微小環境によるγδT細胞免疫疲弊にTim-3分子が関与する事を明らかにした。Tim-3分子の抗体を投与することがγδT細胞細胞療法の癌細胞の治療効果を高める結果、本経路を標的としたTMEに対する免疫アプローチが、膀胱癌のみならず他固形癌に対してのより有効なγδT細胞免疫細胞療法の確立への基盤構築となることが期待される。