Transcriptional profiling of skin cancer NK cells reveals the elevated glucocorticoid receptor activity alters their pro-inflammatory features.

The interplay between natural killer (NK) cells and tumor microenvironment (TME) is closely associated with tumor progression. We showed NK cells are common constituents in the tissue of skin cancers including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), extramammary paget disease (EMPD) and acral melanoma (aMM). scRNA-Seq revealed an inter and intra-tumor transcriptional heterogeneity of NK cells in different skin TMEs. Unexpectedly, compared to peri-tumor, skin tumor NK cells down regulated the production of anti-tumor cytokines, IFN-γ and TNF-α, and up regulated the production of amphiregulin (AREG), a ligand of epidermal growth factor receptor (EGFR), which functions in promoting skin tumor growth and mediating immune tolerance.