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

• 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
• ISSN: 26433230
• HANDLE: 2433/265164
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles