T-cells specific for KSHV and HIV migrate to Kaposi sarcoma tumors and persist over time.

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Tác giả: Lauri D Aicher, Prisca Atwinirembabazi, David G Coffey, Lichen Jing, James Kafeero, David M Koelle, Chris P Miller, Peter Mooka, Dennis Mubiru, Janet Nankoma, Lazarus Okoche, Joseph Okonye, Warren T Phipps, Shashidhar Ravishankar, Semei Sekitene, Iyabode L Tiamiyu, Andrea M H Towlerton, Edus H Warren, Jessica White

Ngôn ngữ: eng

Ký hiệu phân loại: 621.384197 Electrical, magnetic, optical, communications, computer engineering; electronics, lighting

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 676819

UNLABELLED: Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi sarcoma (KS), which causes significant morbidity and mortality worldwide, particularly in people living with HIV (PLWH) and in sub-Saharan Africa where KSHV seroprevalence is high. Postulating that T-cells specific for KSHV and HIV would be attracted to KS tumors, we performed transcriptional profiling and T-cell receptor (TCR) repertoire analysis of tumor biopsies from 144 Ugandan adults with KS, 106 of whom were also living with HIV. We show that CD8 AUTHOR SUMMARY: In this work, we set out to examine Kaposi Sarcoma (KS) tumor tissue, as well as peripheral blood cells from individuals with KS, both living with and without HIV. Our goal was to identify T-cells that specifically recognize antigens encoded by Kaposi sarcoma-associated herpesvirus (KSHV) or HIV. By analyzing the T-cell repertoire in KS tumor biopsies from people in Uganda with different types of KS, we uncovered clusters of T-cells with previously unknown ability to recognize these viruses. Through single-cell sequencing of peripheral blood cells, we also observed that many of these T-cells had cell-killing properties. Notably, they often coexisted with a subset of macrophages with immunosuppressive properties, which we suspect may be suppressing the function of virus-targeting T-cells. Our findings suggest that additional studies of these virus-targeting T-cells and their interaction with immunosuppressive macrophages could significantly advance the development of effective therapeutics against KS.
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