Elucidating the differentiation mechanisms of PD-1 positive regulatory T cells in the tumor microenvironment by single-cell analysis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Irie Takuma 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (50625944)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 制御性T細胞 / 腫瘍浸潤T細胞 / シングルセル解析 / scRNA-seq / scATAC-seq

Outline of Final Research Achievements

Through analysis of clinical samples treated with immune checkpoint inhibitors, our laboratory has found PD-1-positive regulatory T cells to be an important biomarker to predict efficacy. However, there are few studies on tumor-infiltrating PD-1-positive regulatory T cells, the mechanisms of differentiation leading to their characteristic phenotype and their differences from other regulatory T cells. In this study, through single-cell analysis of tumor-infiltrating regulatory T cells, we show that the transcription factor BATF functions as the core of a transcription factor network that differentiates into PD-1-positive regulatory T cells within tumors.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、転写因子BATFが、がん組織内の制御性T細胞のクロマチンのリモデリングに重要であり、　制御性T細胞の活性化プログラムの中核を担っていることを発見した。本研究による成果は、がん組織内の制御性T細胞を標的とする免疫治療開発や制御性T細胞が発症に関わる自己免疫性疾患の理解、様々な医学研究に応用されることが期待される。