The exploration of novel biomarkers and molecular tagets in intrahepatic cholangiocarcinoma based on epigenetic analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18121
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Okayama University
• Principal Investigator: Kazuhiro Yoshida 岡山大学, 医学部, 客員研究員 (60824761)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 肝内胆管癌 / 制御性T細胞 / 細胞障害性T細胞 / 抑制性免疫環境 / FCR

Outline of Final Research Achievements

Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma(ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC. Highly immunogenic ICCs identified in the public dataset and the Cancer Immunome Atlas (TCIA) were assessed to determine the prognostic impact of immunogenicity in ICC and key components after curative resection. We also investigated the clinical relevance of the immune milieu in ICC.
Using the Gene Expression Omnibus dataset and TCIA, we identified CD8+/forkhead box P3 (FoxP3)+ tumourinfiltrating lymphocytes (TILs) in highly immunogenic ICCs. Immunohistochemical analysis of the in-house cohort showed that intratumoral FoxP3+ TILs correlated with CD8+ TILs and that high FoxP3+/CD8+ ratio (FCR) was an important marker for poor survival. Furthermore, the FCR was higher in tumour-free lymph nodes in ICCs with lymph node metastases than in those without lymph node metastases.

Free Research Field

腫瘍制御学

Academic Significance and Societal Importance of the Research Achievements

今後の肝内胆管癌の治療において、腫瘍免疫環境が重要な因子であり、治療標的となりうることを示唆するものと考えられる。特に、胆道癌に対して昨今では、免疫治療が積極的に導入される一方で、高額な治療薬をすべての胆道癌患者に導入することは医療経済学的も問題となり、より治療効果の高い患者群を選別する必要がある。そのなかで、肝内胆管癌の抑制性免疫環境が治療標的となりうることを鑑みると、本研究で提唱した腫瘍免疫環境は個別化医療に応用できる指標となりうると考えられる。