Oncolytic viruses and cytokine-based gene therapies reprogram the tumor microenvironment

Solid tumors are sustained by profoundly immunosuppressive tumor microenvironments (TMEs) that underlie resistance to immunotherapy. Engineered oncolytic viruses and cytokine-based gene therapies can reprogram the TME, converting 'cold' tumors into immune-responsive states and amplifying antitumor immunity. Several agents have achieved regulatory approval, and clinical studies demonstrate that even limited dosing can induce durable changes in immune infiltration and cytokine signaling. Yet consistent and lasting clinical responses remain elusive. Here, we synthesize translational insights from recent trials and highlight emerging strategies to overcome barriers and enhance the therapeutic impact of these TME-modulating biologics.