Understanding the Tumor Microenvironment of Angiosarcoma Prevalent in Okinawa Prefecture and Identifying Tumor Genome Mutations as Therapeutic Targets

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16266
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: AWAZAWA RYOKO 琉球大学, 医学(系)研究科(研究院), 客員研究員 (20457675)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 血管肉腫 / カポジ肉腫 / 琉球諸島 / 宮古諸島 / 血管内皮細胞

Outline of Final Research Achievements

Through comparative group analyses of transcriptome and full-exome data from angiosarcoma and Kaposi's sarcoma, which predominantly occur in Okinawa Prefecture, the immune microenvironment and driver mutations were comprehensively analyzed, particularly in angiosarcomas, and the best therapeutic targets were selected from a number of novel immune checkpoint inhibitors. Gene expression of the CD47-SIRPα system, a checkpoint factor of the innate immune system that inhibits macrophage phagocytosis, was significantly higher in the poor prognosis group. The expressions of immune checkpoint inhibitory proteins in tumor tissue continues to be confirmed by immunohistochemistry. Tumor driver mutations are also being analyzed for correlation with clinical information in angiosarcoma and Kaposi's sarcoma.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究課題は、世界でも稀にみる大規模の単施設コホートを用いた頭部血管肉腫の統合的遺伝子解析で、遺伝子変異のみならず腫瘍微小環境を標的にした遺伝子発現解析も行った。微小環境の正確なプロファイルを得るために、ストップコドン、フレームシフト、エクソンスキップ等の機能的な蛋白発現のないと考えられる変異RNA発現配列を削除した機能的発現遺伝子に限定した独特のアルゴリズムを用いた。これにより、続々と開発される新規の免疫チェックポイント阻害薬から、各希少腫瘍にも既存の検体で最適標的を選択しえる、将来の治療へ直結する解析手法である。