| Project/Area Number |
22K07286
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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 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 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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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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