Oncolytic viral therapy under type I interferon regulation: Mathematical modeling and analysis

We present and analyze a delay differential equation model of oncolytic viral therapy (OVT) that incorporates tumor-immune-virus interactions, type I interferon (IFN-I) dynamics, and a discrete time delay representing the viral infection cycle. Analytical and numerical results reveal that treatment efficacy critically depends on the balance among viral infectivity, IFN-mediated viral suppression, and immune recruitment. In the absence of immune cells, IFN-I can suppress viral replication, while intracellular delay destabilizes tumor-virus coexistence via Hopf bifurcation. When immune response is included, the system exhibits multiple equilibria and rich bifurcation structures, including bistability and codimension-two bifurcation points. Global sensitivity analysis identifies IFN production, IFN-induced immune suppression, viral infectivity, and immune proliferation as key drivers of tumor control. Our results highlight the dual role of IFN-I, which can either promote viral clearance and tumor escape or facilitate viral persistence and improved therapeutic outcome, depending on the context. These findings underscore the importance of personalized strategies that account for IFN signaling, immune strength, and viral dynamics in optimizing OVT efficacy.