Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets

Journal article

BACKGROUND: Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown. OBJECTIVES: The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq). METHODS: scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules. RESULTS: scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1β. AREG and PLAUR were expressed in the CD68+CD163+IL-1β+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1β- subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163-IL-1β+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1β, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume. CONCLUSIONS: Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS

Authors: Baruah, P; Mahony, C; Marshall, JL; Smith, CG; Monksfield, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: British Journal of Cancer
• Volume: 130
• Issue: 10
• Pages: 1659-1669
• Publication date: 2024-03-13
• DOI: 10.1038/s41416-024-02646-2
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English
• Keywords: Genetics; CD163; CD68; Pathogenesis; Pathology; Gene; Immunology; Biology; Gene expression; Flow cytometry; CD14; Phenotype; Macrophage; Immunohistochemistry; Medicine