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

• DOI: 10.1158/2643-3230.c.6550432.v1
• Publication Date: 2023-04-04T19:38:56Z
• Authors: 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 Togashi; Seishi Ogawa; Kazuya Shimoda; Keisuke Kataoka

<div>Abstract<p>Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)–infected cells occurs before viral carcinogenesis. Here we characterize premalignant and the multicellular ecosystem in HTLV-1 infection with without adult leukemia/lymphoma (ATL) by genome sequencing single-cell simultaneous transcriptome T/B-cell receptor surface protein analysis. We distinguish malignant phenotypes caused leukemogenesis dissect evolution different clinical behavior. Within HTLV-1–infected cells, a regulatory phenotype associates expansion. also delineate differences between virus- tumor-related changes nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In newly generated conditional knockout mouse model recapitulating T-cell–restricted <i>CD274</i> (encoding PD-L1) gene lesions found ATL, demonstrate that PD-L1 overexpressed T is transferred to surrounding leading their upregulation. Our findings provide insights into immune landscape multistep carcinogenesis.</p>Significance:<p>Our multimodal analyses comprehensively cellular molecular alterations peripheral blood infection, progression leukemia. This study not only sheds light on carcinogenesis, but helps devise novel diagnostic therapeutic strategies for HTLV-1–related disorders.</p><p><i>This article highlighted Issue feature, p. 403</i></p></div>