Analysis of TCGA glioblastoma datasets demonstrated that interferon-associated transcriptional programs are present across human tumors and are positively associated with PI3K-AKT pathway activity across molecular subtypes.<h4>Conclusions</h4>Together, these findings reveal that chronic IFN-γ exposure drives distinct, lineage-dependent adaptive states in GBM, linking interferon signaling to divergent survival and immune-modulatory programs. Here, AKT1 is linked to glioblastoma.