Analysis of the mechanism of anti-tumor immunosuppression by peritoneal mesothelial cells phagocytosed with ovarian cancer cells and investigation of the method for reactivation anti-tumor immunity

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya University
• Principal Investigator: Koya Yoshihiro 名古屋大学, 医学系研究科, 特任講師 (80396960)
• Co-Investigator(Kenkyū-buntansha): 梶山 広明 名古屋大学, 医学系研究科, 教授 (00345886) ; 吉原 雅人 名古屋大学, 医学部附属病院, 病院助教 (00878374)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腫瘍微小環境 / 腫瘍免疫 / 卵巣癌 / 中皮細胞 / 貪食 / 転移浸潤 / CSPG4 / NGFR

Outline of Final Research Achievements

Mesothelial cells (MCs) are the largest component of the peritoneal cavity and have been reported to have phagocytic capacity. In this study, we evaluated whether MCs exhibit phagocytosis against cancer cells and what kind of changes occur in phagocytosed MCs. The results showed that MCs have phagocytic activity against cell fragments of apoptotic cancer cells, and that the gene expression of molecules that induce immunosuppression was increased in MCs that phagocytosed these cancer cell fragments. It was suggested that phagocytosed MCs may contribute to the evasion of ovarian cancer cells from host antitumor immunity. We also found and evaluated cell surface molecules on the cancer cells. The results showed that these molecules are involved in invasive capacity, proliferative capacity, and spheroid formation.

Free Research Field

腫瘍学、免疫学

Academic Significance and Societal Importance of the Research Achievements

卵巣癌は婦人科系腫瘍の中で最も死亡数が多く、その一因として、腹膜播種という転移様式が挙げられる。腹膜播種の制御が非常に重要である卵巣癌において、腹腔内での腫瘍免疫の制御と賦活化を可能とする、新たな機序と治療戦略を探索する意義は大きい。腹膜は中皮細胞と結合組織から成り、中皮細胞は異物などを取り込む性質を持ち、恒常性の維持に関与している。腹腔内での中皮細胞による抗腫瘍免疫制御に関する報告はこれまでに無く、学術的意義も大きい。また、癌細胞上の分子の新たな機能を明らかにしたことにより、癌悪性化の理解や治療法開発に寄与をした。