Basic study of anti-tumor immunity induction by CDK4 / 6 inhibitor for hepatocellular carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07944
• 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: Nagasaki University
• Principal Investigator: NAKAO Kazuhiko 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00264218)
• Co-Investigator(Kenkyū-buntansha): 玉田 陽子 長崎大学, 病院(医学系), 助教 (70393460)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝癌 / CDK4/6阻害薬 / 抗腫瘍効果

Outline of Final Research Achievements

Addition of a CDK4 / 6 inhibitor to the human liver cancer cell line HuH-7 induced G1 arrest, dephosphorylation of RB protein, and decreased E2F activity. In PLC / PRF / 5, the degree of G1 arrest was weak, and dephosphorylation of RB protein and decrease in E2F activity were also mild. In HuH-7, the production of IFNλ was confirmed by the addition of a CDK4 / 6 inhibitor, and the expression of PKR mRNA was confirmed to be increased. When HuH-7 was treated with a CDK4 / 6 inhibitor, the expression of MHC class I / β-2 MG and PDL-1 on the cell surface was increased. When mouse hepatocellular carcinoma cells were subcutaneously transplanted into allogeneic mice to form a tumor, and then a CDK4 / 6 inhibitor was administered, tumor growth suppression was observed.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

CDK4/6阻害薬は肝癌細胞に対して直接的抗腫瘍効果を示すことが確認された。また、CDK4/6阻害薬は肝癌細胞が宿主の免疫系細胞に標的として認識されやすくする作用を持つことが示唆された。本研究は、対象を乳癌から肝細胞癌に替えただけの検証的な研究ではあるが、CDK4/6阻害薬が乳癌同様、肝癌に於いても抗腫瘍免疫増強効果を持つ可能性が示唆された意義は大きいと考える。