Our data suggest that loss of CXCR2 signaling may reduce sub-populations of melanoma cells expressing the stem cell marker Esrrb but increases populations with the stemness markers Klf4, Hmga1, and Tfcp2l1. Moreover, the gene expression pattern in the six functionally enriched states of tumor cells previously established by single-cell transcriptomics: melanocytic, neural crest-like, antigen-presenting, RNA processing, stem-like, and stress-like, appear to be altered with loss of Cxcr2 signaling, especially in the melanocytic state [56]. This evidence concerns the gene KLF4 and melanoma.