Fig. 4

Origin of wild-type CYSLTR2 expression in uveal melanomas analysed by bulk and single cell RNA sequencing. a Heatmap of row-scaled, normalised log₂(RSEM+ 1) gene expression levels of CYSLTR2, CD14 and CD163 (monocytes/macrophages) and CD3D and CD8A (T cells) as determined by bulk RNA sequencing in 77 wild-type primary uveal melanomas from the TCGA cohort. The highest CYSLTR2 expression levels are observed in the tumours with this immune gene expression signature. b Percentage CYSLTR2 expressing cells per tumour annotated for cell type, as determined by single cell RNA sequencing in eight primary and three metastatic uveal melanomas from the Durante cohort. In 6/11 tumours CYSLTR2 was expressed in > 2% of the cells, which were predominantly melanoma cells. c tSNE plot of single cell RNA sequencing data derived from UMM066, with annotation of clusters for cell type and expression levels per cell of CYSLTR2 (leukotriene receptor), MITF (pigmentation), ETV5 (MAPK activation) and ALOX5AP (leukotriene synthesis). CYSLTR2 was expressed in a subpopulation of melanoma cells that presented with high expression of genes involved in pigmentation and marker genes of MAPK activation. Enzymes catalysing the synthesis of leukotrienes (ligand of CysLT₂R) are expressed by tumour-associated immune cells. Complete tSNE gene expression plots are presented in Supplementary Fig. 4