2023 Fiscal Year Final Research Report
Research on tumor microenvironment modification by combined use of metformin and fasting
| Project/Area Number |
21K19409
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
工藤 生 岡山大学, 医歯薬学域, 助教 (40830378)
西田 充香子 岡山大学, 医歯薬学域, 助教 (60844644)
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| Project Period (FY) |
2021-07-09 – 2024-03-31
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| Keywords | 腫瘍血管 / 代謝 / 一酸化窒素 / 腫瘍浸潤CD8T細胞 / インターフェロンγ / 低酸素 |
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| Outline of Final Research Achievements |
It has been reported that when cancer patients undergo intermittent fasting, their tumors may shrink in occasion. We recently found that the combination of fasting and metformin treatment may have a strong antitumor effect, compared to monotherapy alone. In this study, we were able to clarify part of the underlying molecular mechanism. The excellent antitumor effect observed when metformin is combined with fasting is due to normalization the tumor vessels via suppression of glycolysis in tumor vascular endothelial cells, and the enhanced infiltration of CD8T lymphocytes to tumor due to oxygenation of the tumor microenvironment (reduction in HIF1α expression) associated with blood vessel normalization. The main causes were thought to be an increase in the influx of CD8T cells (CD8TIL), their enhanced interferon γ production, and a decrease in the number of Foxp3+ cells.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
癌患者が間歇的絶食を行うことで腫瘍が縮小する場合があることが報告されている。癌細胞にグルコースをはじめとする栄養素を与えないとする兵糧攻めがそのメカニズムの一つだと考えられている。我々の今回の研究は、絶食にメトホルミン投与を併用することで、より強力な抗腫瘍効果を発揮する可能性を新たに見出した。その分子機構の一端として、腫瘍血管内皮細胞の正常化、それに伴う腫瘍微小環境の酸素化、さらには免疫CD8T細胞の腫瘍への流入増加とインターフェロンγ産生の亢進、制御性T細胞の減少が主な原因である事が示された。間歇的絶食による抗腫瘍効果メカニズムの理解を助けるに資するエビデンスを得ることができた。
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