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.
CITATION STYLE
Koya, J., Saito, Y., Kameda, T., Kogure, Y., Yuasa, M., Nagasaki, J., … Kataoka, K. (2021). Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1. Blood Cancer Discovery, 2(5), 450–467. https://doi.org/10.1158/2643-3230.BCD-21-0044
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