In analogy to what has been recently reported for another GBM-derived molecule, osteopontin, which regulates glioma cell invasiveness and tumor growth (44) and the pro-tumorigenic reprogramming of microglia (45), we demonstrate that soluble CXCL16 released by glioma cells drives GBM growth directly promoting tumor cell proliferation, invasion, and acting on GAMs establishing a pro-tumor microenvironment. The gene discussed is SPP1; the disease is central nervous system cancer.