Elucidation of the role of NKG2D ligands in HBV-related hepatocellular carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07996
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Chiba University
• Principal Investigator: Ryosuke MUROYAMA 千葉大学, 大学院医学研究院, 助教 (50549459)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: B型肝炎ウイルス / 肝細胞癌 / 自然免疫システム / NKG2Dリガンド

Outline of Final Research Achievements

Using RNA-seq data from in HBV-related hepatocellular carcinoma (HCC) tissue, we investigated differentially expressed genes, and found that MICA and MICB expression level is up-regulated. In DNA methylation analysis, the promoter region of genes was generally hypo-methylated in HCC tissue, and the abnormal DNA methylation in genes associated with immune response was suggested to be hepatocarcinogenesis. We constructed vectors expressing full-length MICA and ΔN-MICA (MICA with with a truncation at the N-terminus). After introducing them into hepatoma cell line, we measured the expression level of soluble full-length MICA and ΔN-MICA in supernatant of cell culture using ELISA, and found that the ΔN-MICA expression was almost undetected. This results was suggested that the dynamics in liver cells between them was completely different.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

B型肝炎ウイルス（HBV）感染による肝発癌、すなわちB型肝癌に対する有効な治療法の開発は、肝臓病学において、克服すべき最重要課題の1つである。本研究により、B型肝癌組織において、NKG2Dリガンドに属するMICA, MICBの発現上昇が認められ、「NKG2Dリガンド-NK細胞」を含む自然免疫システムに属する遺伝子群の発現変動が起こっていることが明らかとなった。このことは、「NKG2Dリガンド-NK細胞」という自然免疫システムを強化することでB型肝癌を制御する、すなわちB型肝癌に対する新規の免疫療法の開発につながる重要な知見と考えられる。