Study of next-generation immunotherapy for digestive system cancer targeting DGK alpha/zeta

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03724
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Hokkaido University
• Principal Investigator: Taketomi Akinobu 北海道大学, 医学研究院, 教授 (70363364)
• Co-Investigator(Kenkyū-buntansha): 坂根 郁夫 千葉大学, 大学院理学研究院, 教授 (10183815) ; 北村 秀光 北海道大学, 遺伝子病制御研究所, 准教授 (40360531) ; 深井 原 北海道大学, 医学研究院, 特任講師 (60374344)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 消化器がん / 肝細胞がん / DGKα / がん免疫療法 / T細胞 / 樹状細胞

Outline of Final Research Achievements

We have elucidated the mechanism by which DGKα inhibition suppresses tumor growth in a mouse model of hepatocellular carcinoma through its dual antitumor effects of suppressing cancer cell growth and stimulating antitumor immunity via T cell activation, and exerts synergistic antitumor effects when combined with PD-1/PD-L1 inhibition. Furthermore, in the liver cancer model of DGKζ-deficient mice, antitumor activity was enhanced not only by T cells but also by NK cells and dendritic cells as effector cells, elucidating the mechanism by which DGKζ inhibition activates antitumor immunity by targeting multiple immune cells and revealing the possibility of novel cancer immunotherapy. This finding may lead to the development of a novel cancer immunotherapy.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、DGKが新規がん治療標的として、がん細胞増殖だけでなく抗腫瘍免疫に作用して、がんを制御することを明らかにした。この結果はDGKα/ζの制御が新規がん治療として有望である科学的エビデンスを示した。さらに免疫チェックポイント阻害治療のような既存治療との併用治療に適合性があり、臨床応用において既存治療で効果が不十分な腫瘍に対する新たな治療戦略を提供する可能性を示した。