Immune escape mechanism via phosphatidylserine exposure by tumor cells in ovarian cancer chemotherapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21348
• Project/Area Number (Other): 18H06254 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka University
• Principal Investigator: Kawano Mahiru 大阪大学, 医学系研究科, 助教 (30822209)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 卵巣癌 / 化学療法 / マクロファージ / 貪食 / 免疫逃避

Outline of Final Research Achievements

This study was focused on the phagocytosis of tumor cells by macrophages in ovarian cancer tumor micro-environments. First, the expression of scramblases, which control the exposure of phosphatidylserine in apoptotic tumor cells, was examined. However, it was hard to establish the experimental models.
Second, the effect of “don’t eat me” signal molecule CD47 on the phagocytosis was investigated. Ovarian cancer specimen were evaluated pathologically. As a result, strong CD47 immuno-reactivity was associated with significantly less macrophage infiltration and shorter progression free survival. In vitro phagocytosis assay, treatment with exosome inhibitor (GW4869) decreased the CD47 expression in tumor cells and promoted phagocytosis by macrophages. It is suggested that tumor-derived exosome increase the CD47 expression in tumor cells and contribute in evasion from phagocytosis.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、卵巣癌の免疫逃避機構を解明するため、卵巣癌微小環境でのマクロファージによる腫瘍細胞の貪食に焦点を当てた。免疫逃避機構に関する先行研究の多くが、免疫チェックポイント分子を軸にT細胞の役割を解析したものであったため、本研究で自然免疫の役割を解析した学術的意義は大きいと考えられる。
本研究成果を発展させることにより、予後不良である進行卵巣癌の新規標的の解明につながることが期待でき、社会的意義も大きい研究内容である。