Tumor cells with defective interferon antiviral responses

Tumor cells with defective interferon antiviral responses refers to a malignant cellular phenotype characterized by the loss of innate immune signaling pathways, particularly the Type I interferon (IFN) response (Lichty et al., 2014). In healthy cells, the detection of viral components triggers the production of IFN-alpha and IFN-beta, which bind to the IFNAR receptor to activate the JAK-STAT pathway and induce an antiviral state (Snell et al., 2017). Many tumors selectively disable these pathways—through mutations in genes like JAK1, STAT1, or IRF3—to evade the growth-inhibitory and pro-apoptotic effects of IFN (Xia et al., 2016). This specific vulnerability is exploited by oncolytic viruses, such as Talimogene laherparepvec (T-VEC), which can selectively replicate in and lyse these IFN-defective cells while being cleared by the intact defenses of normal tissues (Reid et al., 2016). This target represents a physiological state rather than a single molecule, serving as a critical determinant for the efficacy of viral-based immunotherapies (Bommareddy et al., 2018). By inducing selective oncolysis, these treatments also promote the release of tumor-associated antigens, potentially overcoming local immunosuppression and stimulating a systemic anti-tumor immune response (Kaufman et al., 2015).

Other names

IFN-deficient tumor cellsInterferon-non-responsive cancer cellsDefective IFN-pathway tumor cellsType I IFN signaling-deficient cells

Selective viral replication and oncolysis in cells with impaired Type I interferon-mediated antiviral defenses (Lichty et al., 2014).