Defects in interferon pathways as potential biomarkers of sensitivity to oncolytic viruses

Abstract

Increased sensitivity of cancer cells to viruses is a prerequisite for the success of oncolytic virotherapy. One of the major causes of such a phenotype is the disruption of innate antiviral defenses associated with dysfunction of type 1 interferons (IFNs) that permits unlimited replication of viruses in cancer cells. Defects in IFN pathways help cancer progression by providing additional advantages to tumor cells. However, while these defects promote the survival and accelerated proliferation of malignant cells, they facilitate viral replication and thus enhance the efficiency of viral oncolysis. This review describes a broad spectrum of defects in genes that participate in IFN induction and IFN response pathways. Expression levels and/or functional activities of these genes are frequently low or absent in cancer cells, making them sensitive to virus infection. Therefore, certain specific defects in IFN signaling cascades might serve as potential biomarkers to help in identifying individual cancer patients who are likely to benefit from oncolytic virotherapy.

ADAR1: “Editor-in-Chief” of Cytoplasmic Innate Immunity

“…Therefore, malignant cells with dysfunctional IFN responses have a selective advantage. Moreover, the loss of IFN defenses is thought to form the basis for the cancer selectivity of several oncolytic viruses (136). Three recent studies have shown that deleting ADAR1 in tumor cells can induce lethality (137–139).…”

Newcastle Disease Virus (NDV) Oncolytic Activity in Human Glioma Tumors Is Dependent on CDKN2A-Type I IFN Gene Cluster Codeletion

“…In conclusion, our data highlight the importance of a glioma patient stratification based on the CDKN2A-IFN gene cluster deletion. That new classification could predict the patients that might potentially respond to NDV oncolytic therapy and possibly use it as a sensitivity biomarker to other oncolytic viruses [ 64 ]. For optimal patient management in GBM clinical practice, accurate CDKN2A CNA analysis prior to treatment is recommended to identify potential NDV non-responder patients and exclude them.…”

The Propagation, Quantification, and Storage of Vesicular Stomatitis Virus

“…Infected horses, cattle, and pigs can develop oral vesicular epithelial lesions (Simon, van Rooijen, & Rose, 2010). VSV has served as a model system and research with this virus has shed light on the infectious cycle of negative‐stranded, non‐segmented RNA viruses, virus‐host interaction, interferon (IFN) susceptibility (Matveeva & Chumakov, 2018), and viral evolution (Wagner & Rose, 1996). It has also served as a tool to illustrate fundamental principles in evolutionary biology and population genetics (Suder, Furuyama, Feldmann, Marzi, & de Wit, 2018).…”