CXCL12 and neoplasm: The CXCR4/CXCL12 axis increases metastasis in lung cancer by mediating chemotaxis of CXCR4+ tumor cells against CXCL12-rich secondary sites (bone marrow, liver, brain), which triggers PI3K/AKT, MAPK/ERK, and JAK/STAT signaling and EMT, invasion, and intravasation/extravasation, and establishes an immunosuppressive TME through Tregs, MDSCs, and TAMs recruitment (Wang et al., 2016).