Multi-omic spatial profiling of nasal polyps identifies multiple immune-epithelial cell-ligand receptor interactions 4292

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Abstract Description Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nasal mucosa characterised by a heterogeneous immune cell infiltrate and that is largely unresponsive to clinical management. The pathology of CRSwNP remains poorly understood and new approaches are needed to study this condition. We used CosMx™ Spatial Molecular Imaging (SMI) and CellScape™ Spatial Immune Profiling (SIP) to examine the molecular and proteomic spatial biology of nasal polyps. Methods CosMx SMI was undertaken on formalin-fixed paraffin-embedded sections of sinonasal biopsies. Slides were analysed with the Human 6,000-plex RNA Discovery Panel. CellScape SIP was conducted on serial sections to validate spatial proteomic immune cell signatures. Results Of 116,372 cells profiled and 3,993 genes detected, 15 distinct cell types and 231 pairwise ligand-receptor interactions were identified. T-cell niches and plasma subsets were co-localised near epithelial cells. Pairwise ligand receptor interactions were identified between fibroblasts and plasma cells, T-cells, granulocytes and B-cells. Cellscape SIP confirmed the presence of immune cell types and allowed characterization of immune cell neighbourhoods in the epithelial compartment. Conclusions Our findings advance the understanding of the heterogeneous immune microenvironment in eCRSwNP and identify potential therapeutic targets needed for new treatment options. Funding Sources Collaborative supportive funding from GSK Topic Categories Immune Mechanisms of Human Disease (HUM)

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