Augmenting human gamma delta T cell-based immunotherapy against oral cancer by targeting nutritional genomics
| Project/Area Number |
18K09563
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Osaka Dental University |
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Principal Investigator |
Domae Eisuke 大阪歯科大学, 歯学部, 講師 (50454559)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ヒトVγ9Vδ2 T細胞 / Vγ9Vδ2T細胞 / γδT細胞 / ニュートリゲノミクス / SREBP-2 / ビスホスホネート |
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| Outline of Final Research Achievements |
To develop adopted immunotherapy for oral cancer, we investigated the ability of human Vγ9Vδ2T cells to recognize and kill oral cancer in vitro.
We confirmed eight OSCC cell lines we used expressed BTN3A proteins, kye molecules of phospho-antige sensing by human Vγ9Vδ2T cells. We also confirmed that N-BP pretreated OSCC cell lines activated Vγ9Vδ2T cells and were killed by Vγ9Vδ2T cells.
Next, we examined the effect of nutritional conditions on the cytotoxic activity of Vγ9Vδ2T cells. The cytotoxic activity was increased when lipids were removed from the culture medium or cholesterol was removed from the cancer cell membrane with cyclodextrin. We also confirmed that, under these conditions, the activity of the mevalonate pathway of oral cancer cells was increased. These results suggest that the nutritional status of lipids has a significant influence on the suppression of oral cancer cells by Vγ9Vδ2T cells.
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| Academic Significance and Societal Importance of the Research Achievements |
癌治療において中心的役割を果たす手術療法や放射線療法は、口腔癌治療においては顔貌や口腔機能に障害を伴うことが多いため、口腔癌の免疫療法の潜在的意義は大きい。本研究ではVγ9Vδ2T細胞による口腔癌抑制作用を評価し、癌細胞の栄養状態を制御することによる癌免疫を増強させる可能性を探索した。その結果、口腔癌細胞の微小環境から脂質を欠乏させることにより、メバロン酸経路の活性化を介して、Vγ9Vδ2T細胞を効率的に活性化し、癌細胞を効率的に殺傷することを見出した。Vγ9Vδ2T細胞による口腔癌免疫療法開発において、癌細胞の栄養状態の制御が、癌抑制を効果的にする一因であることが明らかとなった。
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Report
(5 results)
Research Products
(1 results)
