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• W4317434585 abstract "The incidence of human papillomavirus-positive (HPV + ) tonsillar cancer has been sharply rising during the last decades. Myeloid cells represent an appropriate therapeutic target due to their proximity to virus-infected tumor cells, and their ability to orchestrate antigen-specific immunity, within the tonsil. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV + tonsillar cancer. We observed an expansion of the myeloid compartment in HPV + tonsillar cancer, accompanied by interferon-induced cellular responses both in dendritic cells (DCs) and monocyte-macrophages. Our analysis unveiled the existence of four DC lineages, two macrophage polarization processes, and their sequential maturation profiles. Within the DC lineages, we described a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC transcriptional program involving upregulation of interferon-inducible genes. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which give rise to either interferon-activated or CXCL-producing macrophages, the latter enriched in advanced tumor stages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1 and interferon-activated DCs and macrophages on patient survival using gene signature scoring. The current study contributes to the understanding of myeloid ontogeny and dynamics in HPV-driven tonsillar cancer, and highlights myeloid biomarkers that can be used to assess patient prognosis." @default.
• W4317434585 created "2023-01-19" @default.
• W4317434585 creator A5004367868 @default.
• W4317434585 creator A5011734101 @default.
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• W4317434585 creator A5055074976 @default.
• W4317434585 creator A5062186545 @default.
• W4317434585 creator A5065809036 @default.
• W4317434585 creator A5043590900 @default.
• W4317434585 date "2023-01-19" @default.
• W4317434585 modified "2023-10-03" @default.
• W4317434585 title "Single-cell analysis of myeloid cells in HPV+ tonsillar cancer" @default.
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