Molecular mechanisms underlying an immune evasion by cancer cells via cell-to-cell signaling

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Kobe University
• Principal Investigator: Murata Yoji 神戸大学, 医学研究科, 准教授 (60400735)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: がん免疫監視 / がん微小環境 / 細胞間シグナル / マクロファージ / 膜型分子

Outline of Final Research Achievements

In this study, we found that the membrane protein SIRPα functions as a negative regulator of cancer cell phagocytosis by macrophages and their secretion of cytokines involved in the elimination of cancer cells. We also showed that a novel SIRPα-binding peptide specifically bound to SIRPα enhanced the antitumor effect of antibodies against tumor antigens. Furthermore, using an antibody against the membrane proteins SIRPα and SIRPβ, we demonstrated that SIRPβ acted as a positive regulator of macrophage cytotoxic activity toward cancer cells. The antibody was also found to exert an antitumor effect in mouse models of cancer.

Free Research Field

生化学、腫瘍免疫、分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、膜型分子SIRPαがマクロファージのがん細胞に対する殺細胞効果を抑制的に制御する一方で、膜型分子SIRPβが促進的に制御することを示し、SIRPαとSIRPβを介したマクロファージによる新たながん免疫監視とその作用機構の一端を明らかにした。さらに、膜型分子SIRPαに作用するペプチド、また膜型分子SIRPβに作用する抗体が、新たながんの治療薬として利用できる可能性を示した。