| 研究課題/領域番号 |
22K07286
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分50020:腫瘍診断および治療学関連
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| 研究機関 | 国際医療福祉大学 |
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研究代表者 |
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| 研究分担者 |
三沢 彩 国際医療福祉大学, 医学部, 講師 (20598453)
大多 茂樹 国際医療福祉大学, 医学部, 准教授 (20365406)
河上 裕 国際医療福祉大学, 医学部, 教授 (50161287)
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2024年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
2023年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2022年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
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| キーワード | lipid lowering agents / statins / T cell immune function / inhibitory molecules / anti-tumor responses / Immuno-metabolism / Statins / Immunotherapy / tumor microenvironment / Checkpoint inhibitors |
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| 研究開始時の研究の概要 |
Statins (HMG-CoA reductase inhibitors that inhibit cholesterol synthesis) appear to activate anti-tumor T cells and synergized with ICIs in murine tumor models, and the survivals of lung cancer patients taking statins were prolonged in some observation studies. However, the underlying mechanisms of statins for the enhanced anti-tumor responses remain unclear. Understanding the anti-tumor mechanisms of statins from immuno-metabolic aspects would be helpful for the improvement of the currently using immunotherapies such as immune checkpoint inhibitor combination therapy in cancer patients.
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| 研究実績の概要 |
Nowadays, immune checkpoint inhibitor combination therapies have been greatly focused on cancer immunotherapy. Anti-tumor T cells are key effectors and immuno-metabolic modulations in the tumor microenvironment (TME) are good regulators to improve the efficacy of anti-PD1/L1 treatment. The main purpose of this study are (1) to evaluate the immunological roles of statins (HMG-CoA reductase inhibitors) in order to promote the anti-tumor responses, and (2) to study the possible mechanisms of anti-tumor effects of statins. At first, I examined the role of statins on immunological responses of human immune cells, particularly T lymphocytes from human PBMC. I observed that statins prevented the dysfunction of human T cells by suppressing the T cell inhibitory checkpoint molecules.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
The immunological analyses using human PBMC might depend on the availability of blood from healthy donors. However, the current data showed positive findings so that it will be able to perform steadily according to research plans.
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| 今後の研究の推進方策 |
The order of research plans became slightly different due to the results of certain experiments. I examined in vitro study first to observe the effects of statins on human immune cells as our final goal is to obtain the supportive scientific data that can be applicable on human (cancer patients).
As next step, I plan to perform in vivo analysis using tumor bearing mouse models to study the cellular and molecular immunological responses of statins in the tumor microenvironment.
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