Integrated spatial and single cell analysis identifies CCL21+ lymphatic endothelial cells as a driver of a favorable immune environment in acral melanoma

In the current study we undertook integrated single cell RNA-Seq, spatial transcriptomics and multiplexed immunofluorescence to identify potential regulators of the immune environment. Our analyses identified distinct immune habitats at the invasive front, intratumoral regions and areas of distant inflammation across the AM samples.

Two distinct subclasses of endothelial cells were identified, one with an immune-regulating profile (CCL21, IGF1, IL-7, PDPN) that were characteristic of lymphatic endothelial cells (LECs) and a population of vascular endothelial cells (VECs) (SPARCL1, PVLAP, ADGRL4). Cell-cell interaction and correlation analysis showed the CCL21+ LECs to be a strong regulator of the immune microenvironment through communication with dendritic cells (DCs) and CD4+ T cells.