Analysis of cancer immune regulation mechanism by new immune checkpoint molecule Clec4A4

• Project/Area Number: 17K15027
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: University of Miyazaki
• Principal Investigator: UTO Tomofumi 宮崎大学, 医学部, 講師 (10624653)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 腫瘍治療学 / 免疫抑制 / 樹状細胞 / 免疫学

Outline of Final Research Achievements

In this study, I focused on Clec4A4 molecule, which is involved in suppression of immune response during cancer progression, and attempted functional identification of a novel dendritic cell immune checkpoint that negatively regulates cancer immune responses. As a result, tumor progression of melanoma was suppressed in the tumor-bearing Clec4A4 deficient mice as compared with the tumor-bearing wild type mice. This result suggest that Clec4A4 functions as an activation regulatory molecule of dendritic cells and is a new immune checkpoint in the cancer immune responses.

Academic Significance and Societal Importance of the Research Achievements

現在、免疫チェックポイント分子として判明しているものは主としてT細胞発現分子であり、樹状細胞の機能に着目した報告は皆無であることから、新規樹状細胞発現免疫チェックポイント分子の発見は学術的にも社会的にも大きな意義がある。将来の展望として、マウスClec4A4分子のヒトに相当する分子に対する機能阻害抗体の作出等が、新たながん免疫療法に繋がることが強く期待される。