Analysis of the mechanism of liver resident NK cell activation through the EZH2 epigenetic regulations

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10669
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hiroshima University
• Principal Investigator: Ohira Masahiro 広島大学, 病院(医), 助教 (30397947)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肝細胞癌 / ナチュラルキラー細胞 / 肝臓内免疫

Outline of Final Research Achievements

The purpose of this study is to elucidate the activation mechanism of the liver resident natural killer (NK) cells with vigorous antitumor activity. We have created a mouse model that weakens the liver resident NK cells, and clarified the function and differentiation mechanism of the liver resident NK cells by the whole liver irradiation model. Moreover, it was revealed that genetic polymorphisms of antitumor molecules are associated with recurrence of liver cancer. Maintaining the activity of NK cells in the liver by gene regulation would lead to a novel treatment for liver cancer.

Free Research Field

肝・胆・膵外科

Academic Significance and Societal Importance of the Research Achievements

肝臓癌は悪性腫瘍死因の第5位であり、根治的な治療を行っても再発することが多い。抗癌剤治療や放射線治療の効果は限定的であり、新規治療法の開発が急務である。肝臓内に存在する抗腫瘍活性の高いNK細胞は、肝癌や肝臓治療により弱体化する。本研究結果は、遺伝子制御を含めた免疫療法につながる礎となる。肝内在性NK細胞の活性を維持できる治療法は、既存の治療法に上乗せ効果が期待でき肝臓癌治療成績のさらなる向上が見込まれる。