| Project/Area Number |
16K10370
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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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| Research Field |
Radiation science
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中正 恵二 兵庫医科大学, 医学部, 教授 (00217712)
廣田 省三 兵庫医科大学, 医学部, 名誉教授 (20181216)
山門 亨一郎 兵庫医科大学, 医学部, 教授 (20263022)
善本 知広 兵庫医科大学, 医学部, 教授 (60241171)
平田 豊 兵庫医科大学, 医学部, 講師 (10441247)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肝動脈塞栓術 / 低酸素誘導因子 / 免疫チェックポイント / 肝細胞癌 / HIF-1 / PD-L1 / 低酸素応答 / 免疫寛容 / 動脈塞栓術 / CCL17 / CCL28 / ラット肝細胞癌モデル / 放射線 / インターベンショナルラジオジー |
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| Outline of Final Research Achievements |
Hepatic artery embolization (HAE) is a useful therapeutic option in the management of hepatocellular carcinoma (HCC) and other hypervascular liver tumors. However, little is known about the effects of HAE on the immune system.
Through the in vivo and in vitro experiments in this study, several novel findings about HAE and immune system were demonstrated. First, results of our in vivo study showed that HAE enhanced the expression of PD-L1 in the rat orthotopic hepatoma model. Moreover, the expressions of PD-L1 and HIF-1a were positively correlated. Second, our in vitro cell culture study showed that hypoxic stress increases the expression of PD-L1, and those expressions were suppressed by HIF-1a inhibitors such as Rapamaycin and Bortezomib.
Results of those experiments suggests that HAE enhance the expression of PD-L1 by HIF-1 dependent manner. These finding will be useful for the development of new therapeutic approaches such as HAE plus anti-PD-L1 antibody.
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| Academic Significance and Societal Importance of the Research Achievements |
肝動脈塞栓術は、肝細胞癌や多血性肝転移に対する有効な治療だが、依然、再発が多いことが欠点である。本研究の結果、肝動脈塞栓術後の再発機序として、塞栓術後の低酸素刺激によりHIF-1依存性にPD-L1の発現が増加し、がん免疫逃避機構を助長させる可能性が示唆された。よって、動脈塞栓術と抗PD-L1抗体の併用などによる治療効果の改善が期待でき、新たな治療戦略開発への橋渡しとなる研究成果が得られた。
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