This aligns with findings in tumor models in transgenic mice, where it was demonstrated that, although NK and CD4 T cells can have a supportive function, they are less likely to be directly involved in IL-12-mediated anti-tumor immunity.98,99 In the context of human glioma, the VDX trials showed that, besides the IFN-γ signature, predominantly the number of CD8 T cells, and not CD4 T cells, increased at the tumor site.21 Upon local rIL-12 exposure of the GB, the recruited CD8POS T cells differentiated toward a more effector-like state. This evidence concerns the gene IFNG and central nervous system cancer.