Elucidation of molecular mechanisms underlying cancer cell survival and maintenance by the regulation of innate immune functions

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H04807
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Kobe University
• Principal Investigator: Matozaki Takashi 神戸大学, 医学研究科, 特命教授 (80252782)
• Project Period (FY): 2021-04-05 – 2024-03-31
• Keywords: がん微小環境 / 腫瘍免疫 / マクロファージ / 樹状細胞 / SIRPα

Outline of Final Research Achievements

We have previously shown that the CD47-SIRPα signaling system, a cell-to-cell signaling system, plays a critical role in regulating immune responses in innate immune cells such as dendritic cells and macrophages. In the study, we aimed to elucidate how cancer cells evade immune surveillance by innate immune cells in the tumor microenvironment to achieve their survival and maintenance. In addition, we aimed to establish an innovative cancer treatment method by controlling the function of innate immune cells. We have found a novel regulatory mechanism of immune surveillance against cancer cells by innate immune cells through the CD47-SIRPα intercellular signaling system and SIRPβ, a family molecule of SIRPα. In addition, we have shown that monotherapy with anti-SIRPα/β antibodies may be a potential strategy for cancer immunotherapy.

Free Research Field

基礎医学

Academic Significance and Societal Importance of the Research Achievements

本研究では、がん細胞に対する樹状細胞やマクロファージなどの自然免疫細胞による免疫監視の作用機構の解明に取り組み、がん細胞または獲得免疫細胞と自然免疫細胞間で形成される膜型分子を介した新規の免疫監視の作用機構の一端を明らかにすることができた。今後、さらなる研究を通じて、自然免疫細胞によるがん免疫監視機構の全容の理解とそれを利用した新規がん治療薬の開発につながることが期待できる。