Accumulating evidence has shown that the trace metal elements such as manganese (Mn), copper (Cu), and iron (Fe) play unexpected roles in immune regulation and tumorigenesis.[20, 36, 37] Among these, copper has been demonstrated by our group and others to play oncogenic roles, particularly by directly binding to MEK, PDK1, and ULK to activate downstream signaling pathways such as ERK, AKT, and autophagy, thereby promoting tumor growth in melanoma, breast cancer and NSCLC.[14, 15, 16] However, the influence of copper on the tumor microenvironment (TME) has not been well explored. This evidence concerns the gene PDK1 and melanoma.