2022 Fiscal Year Final Research Report
Elucidation of anti-tumor mechanisms based on innate immune activation by PHD inhibitors and exploration of therapeutic targets
| Project/Area Number |
20K07072
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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 47040:Pharmacology-related
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| Research Institution | Osaka Metropolitan University (2022)
Osaka City University (2020-2021) |
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Principal Investigator |
Tomita Shuhei 大阪公立大学, 大学院医学研究科, 教授 (00263898)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | HIF-PH阻害薬 / 低酸素 / 腫瘍免疫 / マクロファージ / 自然免疫 |
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| Outline of Final Research Achievements |
We found that HIF-PH inhibitors, which enhance HIF signaling, inhibit tumor growth and prolong survival by directly acting on the Mφ subpopulation within the tumor in an animal model of tumor transplantation. The aim of this study was to elucidate the mechanism by which PHD-HIF signaling activation promotes phagocytosis of Ly6CloMφ in tumors. As a result, we screened for the key relevant functional molecules and identified HIF-induced Phagocytosis Factor (HiPAF) as a candidate molecule that contributes to the promotion of phagocytosis induced in Ly6CloMφ in tumors by the activation of PHD-HIF signaling.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の遂行は、現在の腫瘍免疫療法では難治性を示すがんに対して，自然免疫の活性化過程を標的とした新しい腫瘍免疫療法を創出する可能性を有しており、新規創薬研究分野にも繋がることが期待される。
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