2022 Fiscal Year Research-status Report
Identification of novel targets for cancer immunotherapy through investigation of statins` lipid modulating activities on anti-tumor T cells
| Project/Area Number |
22K07286
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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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| Keywords | lipid lowering agents / statins / T cell immune function / inhibitory molecules / anti-tumor responses |
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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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| Causes of Carryover |
In academic year 2023, I would like to investigate the anti-tumor effect of statins using tumor bearing mouse models treated with anti-PD-1 antibody and statins combination therapy. I will also continue in vitro analysis of immunological responses of statins on human immune cells to estimate the possible cellular mechanisms of statins in cancer patients.
Therefore, I will spend research fund to purchase laboratory mice, culture medium, reagents and some antibodies for immunological analysis. I also need to purchase the commercially available statin compound for the in vivo experiments.
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