Inhibition mechanism of peritoneal dissemination of cancer-derived exosomes by innate immune system

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15315
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Tokuda Aya 滋賀医科大学, 医学部, 特任助教 (80814392)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 自然免疫 / 大腸癌

Outline of Final Research Achievements

We collected exosomes from CT26 cells, a mouse-derived colon cancer cell line, and investigated the effect of exosomes on macrophages. When mouse-derived spleen cells were stimulated with CT26-derived exosomes, the production of IFNgamma was increased, suggesting that CT26-derived exosomes activate NK cells. Cytokine array showed an increase in chemokines and IFN-gamma in response to cancer-derived exosome. Stimulation of mouse intraperitoneal cells with cancer-derived exosomes increased the mRNA level of iNOS, suggesting that exosomes promote the differentiation of intraperitoneal macrophages into M1.

Free Research Field

自然免疫

Academic Significance and Societal Importance of the Research Achievements

エクソソームは、癌の増殖や転移に関わるとされ、癌細胞由来のエクソソームが特定の臓器に取り込まれることで転移前ニッチェの形成に関わるとの報告がある。しかし、これらのエクソソームが 癌進展における自然免疫への役割については未だ明らかではない。今回、大腸がんモデルマウスのCT26大腸がん由来のエクソソームを腹腔内投与することで、NK細胞によるIFNγの産生が促進された。これらのエクソソームによる免疫の活性化は機序は、まだ明らかではないが、今後、他の癌種の腹膜転移を抑制する新しい戦略を設計する上で有益であると考えられる。