Changes in the surrounding immune response to malignant transformation of refractory biliary tract cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17645
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Yoshihara Terukazu 大阪大学, 大学院医学系研究科, 招へい教員 (70850311)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 胆道癌 / 免疫反応

Outline of Final Research Achievements

In biliary tract cancer, IL-6 and TGFβ mutually stimulate each other, inducing chemotherapy resistance and cancer metastasis. On the other hand, in inflammatory tissues, the same cytokines induce heterogeneous differentiation of T lymphocytes, which may lead to intratumor heterogeneity of cytokines and localization phenomenon of differentiated T lymphocytes during cancer progression. We investigated this mechanism. In vitro, we established a chemotherapy-resistant strain with similar characteristics to the infiltrating strain and co-cultured it with undifferentiated T cells. When co-cultured with undifferentiated T cells, the T-cell differentiation was observed to differ from that of the parental strain.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

胆道癌におけるリンパ球の腫瘍内局在を検討した初めての研究であり、分化T細胞の局在により予後が異なることを初めて示した。さらに、in vitroでその現象を確認した。胆道癌における薬物療法では、免疫チェックポイント阻害剤が効果的であるため、今後こられの知見が治療法の選択に役立つ可能性がある。薬物療法では、免疫チェックポイント阻害剤を１次治療に用いる方法と２次治療に用いる方法と考えられるが、in vitro実験の結果からは,
同等の治療成績が得られる可能性がある。