In this paper we report for the first time that: (i) CXCL16 drives microglia toward an anti-inflammatory phenotype, able to counteract inflammatory conditions “in vitro”; (ii) CXCL16 released by glioma cells drives GAMs polarization toward an anti-inflammatory phenotype which is determinant to promote glioma progression; (iii) CXCL16 released by tumor cells contributes to glioma cell proliferation, migration, and invasion of brain parenchyma. The gene discussed is CXCL16; the disease is glioma.