Development of personalized treatment by stratification targeting the microenvironment of ovarian cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16769
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Research Institute, Shiga Medical Center (2019); Kyoto University (2018)
• Principal Investigator: Murakami Ryusuke 滋賀県立総合病院(研究所), その他部局等, 医長 (40782363)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 卵巣癌 / 腫瘍微小環境 / トランスレーショナルリサーチ / CD276

Outline of Final Research Achievements

We reported that histopathological classification based on tumor microenvironment reflecting the gene expression profile of high-grade serous ovarian cancer was associated with prognosis and treatment sensitivity. Analysis of the gene expression profiles of the Immune Reactive type with the best prognosis and the Mesenchymal Transition with the poorest prognosis revealed that the immune checkpoint molecule CD276 is highly expressed in tumors and stroma with poor prognosis. We verified that CD276 not only suppresses direct T cell activity as an immunosuppressive factor but also induces M2 macrophages, which are immunosuppressive cells, through the expression of CCL2 in ovarian cancer innate immunized mice. I devise treatments that control the immunosuppressive pathways.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

予後不良な卵巣高異型度漿液性癌のMesenchymal Transitionにおいて、免疫抑制が腫瘍微小環境で高発現しているCD276により、直接的な活性化Tリンパ球への抑制効果と、間接的に免疫抑制系細胞であるM2マクロファージを誘導することで、免疫抑制環境をより強くさせていることを発見した。本研究で、難治性な卵巣癌に対して複数の免疫抑制経路を遮断する治療がより有効な治療戦略であることが示唆された。