Antitumor immunity mediated by HLA-E in hepatocellular carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22760
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Nakagawa Hidetoshi 金沢大学, 医学系, 助教 (90743469)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: HLA-E / 肝細胞癌

Outline of Final Research Achievements

This study has identified and uncovered aspects of the immune response mediated by HLA-E, which had not been fully elucidated until now. Examination of surgical specimens revealed HLA-E expression in some hepatocellular carcinoma cells, but primarily in tumor-infiltrating immune cells. Furthermore, in the examination of peripheral blood, HLA-E was expressed in immune cells in general. Further analysis led to the identification of candidate T cell receptors that recognize HLA-E.
In the examination of cases of immunotherapy for liver cancer, it was observed that when the HLA-E haplotype is 0101/0101, there is a trend towards a shorter progression-free survival period. These results suggest that the interaction between HLA-E and a specific group of immune cells may affect the progression of liver cancer and the response to immunotherapy.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

これまで十分に解明されていなかったHLA-Eを介した免疫応答を解析することで、がん治療のみならず、自己免疫疾患の理解の新たな側面を明らかにした。本研究で明らかになったHLA-Eハプロタイプとがん免疫療法の治療効果の関連や、HLA-Eを認識するCD8陽性T細胞の存在、またそのT細胞受容体の同定から、免疫制御の観点からHLA-Eが重要な役割を担っていると考えられた。今後の展開として得られたT細胞受容体の機能解析をすすめ、新たな免疫療法のツールとして利用することを目指す。