The tumor microenvironment and the novel therapy of MYC-associated hepatocellular carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20804
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Taniai Tomohiko 東京慈恵会医科大学, 医学部, 助教 (60961860)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 肝細胞癌 / 癌微小環境 / 複合免疫療法

Outline of Final Research Achievements

Based on comprehensive genome and transcriptome analysis, we established aggressive subtype hepatocellular carcinoma (HCC) cell line by tro53 knockout and MYC overexpression. This cell line showed abnormal cell cycle, and syngeneic mice model showed rapid tumor progression. We performed immunohistochemistry for resected tumor. It revealed immune-cold tumor microenvironment and abnormal vessel structure named vessels encapsulating tumor clusters (VETC). We also performed treatment of lenvatinib for this tumor. Lenvatinib disrupted the formation of VETC and induced tumor infiltrating lymphocytes. These results indicated that MYC-associated hepatocellular carcinoma showed immune-cold tumormicroenvironment, and lenvartinib may regulate the formation of VETC, resulting in the improvement of the efficacy of immune checkpoint inhibitors.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究はMYC過剰発現を特徴とした予後不良な肝細胞癌の癌免疫微小環境の詳細およびその形成過程について明らかにした。また、同腫瘍が示すvessels encapsulating tumor clusters (VETC) と呼ばれる特徴的な異常腫瘍血管構造の形成をレンバチニブが制御する可能性があり、それに伴い免疫不応答な癌微小環境を免疫応答性へと改善させ、免疫チェックポイント阻害剤の奏功改善に寄与する可能性があることを示した。