Establishment of a comprehensive cancer immunotherapy based on whole-genome analysis for treatment-resistant choriocarcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09639
• 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: Niimi Kaoru 名古屋大学, 大学院医学系研究科, 講師 (20571334)
• Co-Investigator(Kenkyū-buntansha): 奥野 友介 名古屋市立大学, 医薬学総合研究院(医学), 教授 (00725533)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 絨毛癌 / 絨毛性腫瘍 / NK細胞 / 全エクソームシークエンス

Outline of Final Research Achievements

We attempted to identify gene mutations by whole-genome analysis of choriocarcinoma tissues using next-generation sequencer. The number of gene mutations in gestational tumors was around 30, while the median number of gene mutations in non-gestational tumors was 150. TP53 gene mutations were observed in two cases of gestational tumors, suggesting the possibility of driver genes for choriocarcinoma. We analyzed the anti-tumor immune response by site of trophoblastic tumors, and found that the NK cell/CD8+ T cell ratio was higher in the tumor than in the peripheral blood, and that the ratio was higher in choriocarcinoma cases than in endometrial cancer cases at the tumor site. We successfully established an in vivo model (Patient-derived xenograft: PDX model) using tumor fatigue from a patient with non-gestational choriocarcinoma.

Free Research Field

絨毛性疾患

Academic Significance and Societal Importance of the Research Achievements

次世代シーケンサーを用いて、実際の絨毛癌臨床検体から遺伝子変異を同定した。稀な絨毛癌の複数の症例で、本人、パートナー、腫瘍を用いて腫瘍に特異的な遺伝子変異を同定することは他では行われておらず、学術的意義のあるものである。非妊娠性絨毛癌患者の腫瘍検体を用いて、in vivoモデル（Patient-derived xenograft: PDXモデル）の作成に成功した。次世代絨毛癌で世界ではじめてPDXモデルの作成に成功した。in vivoでの解析をさらに進めることで、臨床応用の可能性が期待できると考える。