Our study helps shed light on the different roles played by Bcl-xL in melanoma, and elucidates the comprehensive tumor-microenvironment interaction network, demonstrating a pro-tumoral role of Bcl-xL, and indicating that therapies targeting directly Bcl-xL could be able to weaken the crosstalk between tumor and its microenvironment, blocking its progression. Here, BCL2L1 is linked to neoplasm.