In conclusion, our results demonstrate that IGFBP6 modulates polarization of microglia and that its expression is regulated by lactate production in GBM cells suggesting the existence of a lactate to IGFBP6 crosstalk between microglial cells and GBM and this relationship modulates TME, which could affect tumor progression and resistance to therapy and that the complex network of interaction between microglial cells and GBM may represent a potential therapeutic target to overcome tumor malignancy. This evidence concerns the gene IGFBP6 and glioblastoma.