Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1
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- 古屋, 淳史
- Division of Molecular Oncology, National Cancer Center Research Institute
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- 斎藤, 優樹
- Division of Molecular Oncology, National Cancer Center Research Institute; Department of Gastroenterology, Keio University School of Medicine
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- 亀田, 拓郎
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 木暮, 泰寛
- Division of Molecular Oncology, National Cancer Center Research Institute
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- 湯浅, 光博
- Division of Molecular Oncology, National Cancer Center Research Institute; Department of Pathology, Graduate School of Medicine, The University of Tokyo
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- 長崎, 譲慈
- 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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- 新垣, 清登
- Division of Molecular Oncology, National Cancer Center Research Institute
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- 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
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- 田平, 優貴
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 秋月, 渓一
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 上運天, 綾子
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 関根, 雅明
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 幣, 光太郎
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 久冨木, 庸子
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 日高, 智徳
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 北中, 明
- Department of Laboratory Medicine, Kawasaki Medical School
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- 中野, 伸亮
- Department of Hematology, Imamura General Hospital
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- 宇都宮, 與
- Department of Hematology, Imamura General Hospital
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- 冨樫, 庸介
- Chiba Cancer Center, Research Institute
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- 小川, 誠司
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University
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- 下田, 和哉
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki
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- 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
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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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キーワード
詳細情報 詳細情報について
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- CRID
- 1050570852872632960
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- NII論文ID
- 120007145001
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- ISSN
- 26433249
- 26433230
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- HANDLE
- 2433/265164
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- PubMed
- 34661162
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- Crossref
- CiNii Articles
- KAKEN
- OpenAIRE
