Immunogenomic landscape of gynecologic carcinosarcoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07338
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Mori Seiichi 公益財団法人がん研究会, がんプレシジョン医療研究センター 次世代がん研究シーズ育成プロジェクト, プロジェクトリーダー (10334814)
• Co-Investigator(Kenkyū-buntansha): 清谷 一馬 公益財団法人がん研究会, がんプレシジョン医療研究センター 免疫ゲノム医療開発プロジェクト, 主任研究員 (30433642)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 婦人科癌肉腫 / ゲノム情報 / 免疫微小環境 / T細胞受容体レパトワ

Outline of Final Research Achievements

Gynecological carcinosarcoma (CS) is a rare, biphasic tumor comprising epithelial and mesenchymal elements, and exhibits more aggressive clinical features. Four molecular subtypes of CS were recently established (POLE, MSI, CNH, and CNL) and shown to be associated with multiple clinicopathological parameters. However, the role of the immune microenvironment in CS remains unclear. Relying on estimations of tumor-infiltrating cell types from RNA-seq data, POLE and MSI tumors showed an enrichment of M1 macrophages, plasma cells and CD8+ T cells, whereas CNH and CNL tumors had high levels of M2 macrophages. T-cell heterogeneity was independently correlated with prolonged progression-free survival. Differential analysis of carcinoma and sarcoma elements identified many shared mutations but there was little overlap in the T-cell receptor repertoire between the two elements.

Free Research Field

がんゲノム学

Academic Significance and Societal Importance of the Research Achievements

非常に予後の悪い、婦人科癌肉腫がなぜ予後が悪いのか、マルチオミックス情報を取得して、免疫微小環境について検索した。我々の研究により、再発しやすい癌肉腫と再発しにくい癌肉腫の免疫学的な特徴を明らかにした。我々の研究は、一部の癌肉腫に対して有効な治療法を見つけることに貢献できるものと考える。