2022 Fiscal Year Final Research Report
Improve of tumor microenvironment regulate anti-tumor immune response
| Project/Area Number |
20K07295
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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 48030:Pharmacology-related
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| Research Institution | Osaka Metropolitan University (2022)
Osaka City University (2020-2021) |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 腫瘍微小環境 / 低酸素誘導因子 |
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| Outline of Final Research Achievements |
In this study, we investigated the mechanism by which administration of prolyl hydroxylase (PHD) inhibitor suppresses tumor growth by tumor infiltrating macrophages (MΦ) in tumor bearing mice. It was suggested that HIF-1α of MΦ in tumor tissue becomes dominant by administration of PHD inhibitor, which is involved in suppressing tumor growth. dominance of HIF-1α in MΦ was induced enhancing phagocytosis and increasing expression of inflammatory cytokines. In addition, we found a candidate gene that is induced by HIF-1α-dominant MΦ and is involved in tumor suppression. It was implied that upregulation of this gene was mediated by HIF as part of the tumor suppression mechanism by PHD inhibitors.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
一般的にHIF-１αは腫瘍進展に働くとされるが、本研究成果からは生体内において、マクロファージHIF-1αの優位な発現は腫瘍抑制性に作用することが示唆された。PHD阻害薬の腫瘍への影響の一端を明らかにしたと考える。また、治療抵抗性腫瘍などマクロファージ多く存在する癌種ではHIF-1αを優位にすることが治療戦略の１つ候補となる可能性が考えられる。また、HIF-1α下流の遺伝子がその腫瘍抑制に関与していることが示唆されたことから、今後これらの遺伝子機能についてその詳細を解析することで、腫瘍内マクロファージによる腫瘍抑制機序の一端が明らかになるものと考えられる。新規の創薬標的に繋がるものと考える。
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