2022 Fiscal Year Final Research Report
Antitumor effect of histone deacetylase class IIa inhibitor with CIML NK cell in hepatocellular cell carcinoma
Project/Area Number |
21K15954
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Sapporo Medical University |
Principal Investigator |
Kubo Tomohiro 札幌医科大学, 医学部, 助教 (00634669)
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Project Period (FY) |
2021-04-01 – 2023-03-31
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Keywords | CIML NK cell / 選択的Class Ⅱa HDAC阻害薬 / 肝細胞癌 |
Outline of Final Research Achievements |
We evaluated that the antitumor effects of CIML NK cells and their combination with selective inhibitors of HDAC Class IIa, which is highly expressed in hepatocellular cell carcinoma and involved in the regulation of gene expression, in hepatocellular cell carcinoma cell lines. CIML NK cells showed higher cytotoxic activity in hepatocellular cell carcinoma cell lines compared to control NK cells (IL-2 stimulation only). Next we examined changes in gene expression of hepatocellular cell carcinoma cell lines exposure to selective Class IIa HDAC inhibitors, we found that ULBP1 and B7-H6 gene expression, which are ligands for NK cell activation receptors, were decreased. and the cytotoxic activity of CIML NK cells in hepatocellular cell carcinoma cell lines was reduced by concomitant use of selective Class IIa HDAC inhibitors.
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Free Research Field |
腫瘍免疫
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Academic Significance and Societal Importance of the Research Achievements |
CIML NK細胞による免疫療法は、肝細胞癌に対しても高い抗腫瘍効果を示し、新たな治療戦略の一つとなる可能性が示唆されるが、今後、in vivoマウスモデルでの抗腫瘍効果の検討や癌微小環境内においてCIML NK細胞の細胞傷害活性が維持されるかなどについてさらにこの研究を発展させていく必要がある。一方で選択的 Class IIa HDAC阻害薬はCIML NK細胞の細胞傷害活性を減弱させたため、CIML NK細胞の効果を増強する他のepigenetic drugの探索が必要である。
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