Tumor cells with defective antiviral signaling

Tumor cells with defective antiviral signaling represent a phenotypic target class characterized by the loss of innate immune defenses, particularly the Type I interferon (IFN) pathway (Stojdl et al., 2000, Nature Medicine). During oncogenesis, many cancer cells acquire mutations or epigenetic changes in genes such as JAK1, STAT1, or STING to evade immune surveillance and promote survival (Xia et al., 2016, Cell Reports). This defect creates a unique therapeutic window exploited by oncolytic viruses, which are often engineered to be unable to overcome the antiviral responses of healthy cells but can replicate freely in these defective tumor cells (Lichty et al., 2014, Nature Reviews Cancer). As the virus replicates, it causes selective oncolysis, releasing tumor-associated antigens and danger signals that prime the adaptive immune system against the cancer. This approach effectively transforms the immunosuppressive tumor microenvironment into an immunostimulatory one, potentially overcoming resistance to other therapies like checkpoint inhibitors. However, the heterogeneity of these defects across different patients and tumor types remains a significant challenge for ensuring consistent clinical efficacy.

Other names

IFN-deficient tumor cellsInterferon-nonresponsive cancer cellsOncolytic virus-sensitive tumor cellsDefective innate immune signaling in cancerAntiviral-deficient malignant cells

Oncolytic viruses exploit the loss of Type I interferon signaling and other antiviral pathways (e.g., PKR, OAS) in tumor cells to achieve selective viral replication, leading to direct cell lysis (oncolysis) and the induction of a systemic anti-tumor immune response through the release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs).