The pros and cons of interferons for oncolytic virotherapy. (December 2020)

• Record Type: Journal Article
• Authors: Geoffroy, Karen; Bourgeois-Daigneault, Marie-Claude
• Is Part Of: Cytokine & growth factor reviews. Volume 56(2020)
• Page Start: 49
• Page End: 58
• Publication Date: 2020-12
• Subjects: Interferon -- Oncolytic virus -- Cancer -- Anti-tumor immunity -- Immune stimulation -- Inflammation; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2020.07.002
• Languages: English
• ISSNs: 1359-6101

Abstract

Graphical abstract: The pros and cons of interferons for oncolytic virotherapy . Cancer cells have defects in the interferon pathway and shut down the immune response to evade elimination. This is beneficial for oncolytic viruses that can replicate in tumors without the anti-viral effect of interferons. Oncolytic viruses directly target and kill tumor cells while triggering interferon responses that activate both anti-viral and anti-tumoral immune responses. Red lines: inhibition; blue arrows: activation; doted lines: indirect effect and solid lines: direct effect. Highlights: Interferons are essential for the effective control of viruses as well as the induction of anti-tumor immunity. Cancers often have defects in their ability to either produce or respond to IFNs, which makes them sensitive to viruses. Oncolytic viruses trigger the production of interferons. Some engineered oncolytic viruses trigger an even more potent interferon response. They are attenuated, but safer. Oncolytic viruses induce anti-tumor immunity, which is dependent on interferons. Abstract: Interferons (IFN) are potent immune stimulators that play key roles in both innate and adaptive immune responses. They are considered the first line of defense against viral pathogens and can even be used as treatments to boost the immune system. While viruses are usually seen as a threat to the host, an emerging class of cancer therapeutics exploits the natural capacity of some viruses to directly infect and kill cancer cells. The cancer-specificity of these bio-therapeutics, called oncolytic viruses (OVs), often relies on defective IFN responses that are frequently observed in cancer cells, therefore increasing their vulnerability to viruses compared to healthy cells. To ensure the safety of the therapy, many OVs have been engineered to further activate the IFN response. As a consequence of this IFN over-stimulation, the virus is cleared faster by the immune system, which limits direct oncolysis. Importantly, the therapeutic activity of OVs also relies on their capacity to trigger anti-tumor immunity and IFNs are key players in this aspect. Here, we review the complex cancer–virus–anti-tumor immunity interplay and discuss the diverse functions of IFNs for each of these processes.