Altogether, these results suggest that a MAPK-ERK1/2-SP1-GM-CSF signaling node underlies several aspects of cancer cell-intrinsic pro-tumorigenic features, through increasing the abundance of monocyte-derived Ly6Clow cells in the NrasG12D/PtenKO HCC TME and promoting a heightened inflammatory and immunosuppressive phenotype in this immature myeloid cell population. This evidence concerns the gene CSF2 and hepatocellular carcinoma.