Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1

  • 古屋, 淳史
    Division of Molecular Oncology, National Cancer Center Research Institute
  • 斎藤, 優樹
    Division of Molecular Oncology, National Cancer Center Research Institute; Department of Gastroenterology, Keio University School of Medicine
  • 亀田, 拓郎
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 木暮, 泰寛
    Division of Molecular Oncology, National Cancer Center Research Institute
  • 湯浅, 光博
    Division of Molecular Oncology, National Cancer Center Research Institute; Department of Pathology, Graduate School of Medicine, The University of Tokyo
  • 長崎, 譲慈
    Chiba Cancer Center, Research Institute
  • McClure, Marni B.
    Division of Molecular Oncology, National Cancer Center Research Institute
  • 新垣, 清登
    Division of Molecular Oncology, National Cancer Center Research Institute
  • 田畑, 真梨子
    Division of Molecular Oncology, National Cancer Center Research Institute; Department of Urology, Graduate School of Medicine, The University of Tokyo
  • 田平, 優貴
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 秋月, 渓一
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 上運天, 綾子
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 関根, 雅明
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 幣, 光太郎
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 久冨木, 庸子
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 日高, 智徳
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 北中, 明
    Department of Laboratory Medicine, Kawasaki Medical School
  • 中野, 伸亮
    Department of Hematology, Imamura General Hospital
  • 宇都宮, 與
    Department of Hematology, Imamura General Hospital
  • 冨樫, 庸介
    Chiba Cancer Center, Research Institute
  • 小川, 誠司
    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University
  • 下田, 和哉
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • 片岡, 圭亮
    Division of Molecular Oncology, National Cancer Center Research Institute; Division of Hematology, Department of Medicine, Keio University School of Medicine

説明

Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)–infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1–infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell–restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis.

収録刊行物

  • Blood Cancer Discovery

    Blood Cancer Discovery 2 (5), 450-467, 2021-09

    American Association for Cancer Research (AACR)

被引用文献 (3)*注記

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参考文献 (33)*注記

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