Tumor cells with defective antiviral response pathways

Tumor cells with defective antiviral response pathways refers to a common malignant phenotype where innate immune defenses, particularly the Type I Interferon (IFN) signaling pathway, are compromised (Nature Reviews Cancer, 2015, 15:447-466). In normal cells, the detection of viral components triggers the production of IFNs, which bind to receptors (IFNAR1/2) and activate the JAK/STAT signaling cascade to induce an antiviral state characterized by the expression of interferon-stimulated genes (ISGs) that inhibit viral replication. Many tumors acquire defects in these pathways—such as mutations in IFN receptors, loss of STAT1/2, or downregulation of sensors like RIG-I and MDA5—to evade immune surveillance and facilitate rapid proliferation (Frontiers in Immunology, 2020, 11:587). This vulnerability is exploited by oncolytic viruses (OVs), such as Talimogene laherparepvec, which are engineered or naturally predisposed to replicate selectively in cells that cannot mount an effective antiviral response. By selectively infecting and lysing these antiviral-defective tumor cells, OVs provide a dual therapeutic effect: direct tumor destruction (oncolysis) and the subsequent induction of a systemic anti-tumor immune response through the release of tumor-associated antigens and danger signals (Journal of Clinical Investigation, 2007, 117:3148-3150). This strategy allows for targeted therapy that spares healthy, IFN-responsive tissues while overcoming the immunosuppressive environment of the tumor.

Other names

IFN-deficient tumor cellsAntiviral-deficient cancer cellsDefective Type I Interferon pathway tumor cellsOncolytic virus-sensitive tumor cells

Selective viral replication and oncolysis in cells with impaired Type I Interferon or other innate antiviral signaling pathways, followed by induction of systemic anti-tumor immunity.