In cancer microenvironment, both neoplastic and surrounding immune cells may express functional CXCR4, so the downstream G protein and arrestin dependent signaling modules can exert pleiotropic tumor-promoting effects, such as favoring chemotaxis in a Rac1 dependent manner [9], recruiting endothelial progenitors to initiate neoangiogenesis [18] and shaping macrophage polarization towards the immune tolerant M2 phenotype [19]. Here, CXCR4 is linked to cancer.