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

Junji Koya, Yuki Saito, Takuro Kameda, Yasunori Kogure, Mitsuhiro Yuasa, Joji Nagasaki, Marni B. McClure, Sumito Shingaki, Mariko Tabata, Yuki Tahira, Keiichi Akizuki, Ayako Kamiunten, Masaaki Sekine, Kotaro Shide, Yoko Kubuki, Tomonori Hidaka, Akira Kitanaka, Nobuaki Nakano, Atae Utsunomiya, Yosuke TogashiSeishi Ogawa, Kazuya Shimoda, Keisuke Kataoka

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)–abstRact 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.

Original languageEnglish
Pages (from-to)450-467
Number of pages18
JournalBlood cancer discovery
Issue number5
Publication statusPublished - 2021 Sept 1

ASJC Scopus subject areas

  • General Medicine


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