Single-cell RNA profiling of giant cell tumor of bone

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16648
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tsuda Yusuke 東京大学, 医学部附属病院, 助教 (70896018)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: シングルセルRNAシークエンス / Regulatory T cell / 組織微小環境

Outline of Final Research Achievements

A 47-year-old woman underwent surgical excision of clear cell sarcoma in right knee and inguinal lymph node metastasis after neo-adjuvant chemotherapy. However, she died due to liver and para-aortic lymph node metastasis. Single-cell RNA sequencing of the primary tumor and metastatic lymph node samples revealed the accumulation of CTLA4+/CD4+ regulatory and LAG3+/CD8+ exhausted T cells particularly in the metastatic lymph node. NicheNet analysis indicated that these T cell states were induced by the interplay of T cells with tumor cells, macrophages, B cells, fibroblasts, and endothelial cell. The cellular constitution of immune and stromal cell types and their properties suggested the presence of T cell immunosuppression in the clear cell sarcoma microenvironment.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

シングルセル解析により、軟部明細胞肉腫の組織微小環境中の細胞種多様性を明らかにし、免疫細胞を含め異なる細胞種間相互作用を抽出した。免疫抑制的な環境が構築されていることが示唆された。特に、CTLA4+ Tregが増加しており、皮膚メラノーマと同様に抗CTLA4抗体による免疫治療が有効である可能性が考えられた。軟部明細胞肉腫に対するシングルセル解析を行った報告はなく、学術的意義が高い研究である。