How GBM cells respond to sustained IFN-γ signaling, and whether these responses differ across tumor states, remains poorly understood.<h4>Methods</h4>To address this, we modeled chronic IFN-γ exposure in mesenchymal-like (U87) and proneural-like (U251) GBM cells over 28 days and performed integrated analyses of transcriptional, proteomic, and secretory responses.<h4>Results</h4>While IFN-γ initially suppressed growth in both models, their long-term adaptations diverged. The gene discussed is IFNG; the disease is neoplasm.