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

HANDLE Open Access
  • Koya, Junji
    Division of Molecular Oncology, National Cancer Center Research Institute
  • Saito, Yuki
    Division of Molecular Oncology, National Cancer Center Research Institute; Department of Gastroenterology, Keio University School of Medicine
  • Kameda, Takuro
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Kogure, Yasunori
    Division of Molecular Oncology, National Cancer Center Research Institute
  • Yuasa, Mitsuhiro
    Division of Molecular Oncology, National Cancer Center Research Institute; Department of Pathology, Graduate School of Medicine, The University of Tokyo
  • Nagasaki, Joji
    Chiba Cancer Center, Research Institute
  • McClure, Marni B.
    Division of Molecular Oncology, National Cancer Center Research Institute
  • Shingaki, Sumito
    Division of Molecular Oncology, National Cancer Center Research Institute
  • Tabata, Mariko
    Division of Molecular Oncology, National Cancer Center Research Institute; Department of Urology, Graduate School of Medicine, The University of Tokyo
  • Tahira, Yuki
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Akizuki, Keiichi
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Kamiunten, Ayako
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Sekine, Masaaki
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Shide, Kotaro
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Kubuki, Yoko
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Hidaka, Tomonori
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Kitanaka, Akira
    Department of Laboratory Medicine, Kawasaki Medical School
  • Nakano, Nobuaki
    Department of Hematology, Imamura General Hospital
  • Utsunomiya, Atae
    Department of Hematology, Imamura General Hospital
  • Togashi, Yosuke
    Chiba Cancer Center, Research Institute
  • Ogawa, Seishi
    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University
  • Shimoda, Kazuya
    Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
  • Kataoka, Keisuke
    Division of Molecular Oncology, National Cancer Center Research Institute; Division of Hematology, Department of Medicine, Keio University School of Medicine

Abstract

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.

Journal

  • Blood Cancer Discovery

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

    American Association for Cancer Research (AACR)

Details

  • CRID
    1050570852872632960
  • NII Article ID
    120007145001
  • ISSN
    26433249
    26433230
  • HANDLE
    2433/265164
  • Text Lang
    en
  • Article Type
    journal article
  • Data Source
    • IRDB
    • CiNii Articles

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