Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1
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- Koya, Junji
- Division of Molecular Oncology, National Cancer Center Research Institute
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- Saito, Yuki
- Division of Molecular Oncology, National Cancer Center Research Institute; Department of Gastroenterology, Keio University School of Medicine
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- Kameda, Takuro
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Kogure, Yasunori
- Division of Molecular Oncology, National Cancer Center Research Institute
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- Yuasa, Mitsuhiro
- Division of Molecular Oncology, National Cancer Center Research Institute; Department of Pathology, Graduate School of Medicine, The University of Tokyo
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- Nagasaki, Joji
- Chiba Cancer Center, Research Institute
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- McClure, Marni B.
- Division of Molecular Oncology, National Cancer Center Research Institute
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- Shingaki, Sumito
- Division of Molecular Oncology, National Cancer Center Research Institute
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- Tabata, Mariko
- Division of Molecular Oncology, National Cancer Center Research Institute; Department of Urology, Graduate School of Medicine, The University of Tokyo
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- Tahira, Yuki
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Akizuki, Keiichi
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Kamiunten, Ayako
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Sekine, Masaaki
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Shide, Kotaro
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Kubuki, Yoko
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Hidaka, Tomonori
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Kitanaka, Akira
- Department of Laboratory Medicine, Kawasaki Medical School
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- Nakano, Nobuaki
- Department of Hematology, Imamura General Hospital
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- Utsunomiya, Atae
- Department of Hematology, Imamura General Hospital
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- Togashi, Yosuke
- Chiba Cancer Center, Research Institute
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- Ogawa, Seishi
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University
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- Shimoda, Kazuya
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- Kataoka, Keisuke
- Division of Molecular Oncology, National Cancer Center Research Institute; Division of Hematology, Department of Medicine, Keio University School of Medicine
Description
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
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- Blood Cancer Discovery
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Blood Cancer Discovery 2 (5), 450-467, 2021-09
American Association for Cancer Research (AACR)
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Details 詳細情報について
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- CRID
- 1050570852872632960
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- NII Article ID
- 120007145001
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- ISSN
- 26433249
- 26433230
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- HANDLE
- 2433/265164
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles