The Wnt/β-catenin signaling pathway also regulates the differentiation of CD4+ helper T cells [2] and limits the immunosuppressive activity of Treg cells by modulating FOXP3 transcriptional activity, which has been associated with a lack of T-cell infiltration in the TME of metastatic melanoma and other cancer types [43]. This evidence concerns the gene FOXP3 and metastatic melanoma.