Tumor cells with defective type I interferon antiviral signaling (IFN-defective tumor cells)

Tumor cells with defective type I interferon (IFN) antiviral signaling represent a cellular phenotype frequently exploited in oncolytic virotherapy (Nature Reviews Cancer, 2021). In normal physiology, the type I IFN pathway serves as a primary defense against viral infection by inducing an antiviral state through the JAK-STAT signaling cascade and the expression of interferon-stimulated genes (ISGs) (NIH/StatPearls, 2023). Many tumor cells harbor defects in this pathway—such as mutations in STING, cGAS, or JAK1—to evade immune surveillance and apoptosis (Journal of Clinical Investigation, 2019). These defects render the cells selectively susceptible to oncolytic viruses like Talimogene laherparepvec (T-VEC) or Vesicular Stomatitis Virus (VSV), which can replicate efficiently only in the absence of a functional IFN response (Frontiers in Oncology, 2020). Consequently, this "target" is a biological context used for patient stratification and the design of virus-based immunotherapies. The loss of IFN signaling allows viruses to bypass the translational inhibition and RNA degradation that would normally occur in healthy tissue. This selective vulnerability is a hallmark of many solid tumors and is being actively researched to improve the efficacy of viral-mediated gene therapy. Identifying these defects through biomarkers like STING or IRF3 expression helps in selecting patients most likely to benefit from these treatments.

Other names

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

Oncolytic viruses selectively replicate in and lyse these cells because the cells lack the ability to produce or respond to type I interferons, which normally induce an antiviral state that blocks viral protein synthesis and genome replication.