Engineering interferons for cancer immunotherapy

Interferons are a family of cytokines that are famously known for their involvement in innate and adaptive immunity. Type I interferons (IFNs) exert pleiotropic effects on various immune cells and contribute to tumor-intrinsic and extrinsic mechanisms. Their pleiotropic effects and ubiquitous expression on nucleated cells have made them attractive candidates for cytokine engineering to deliver to largely immunosuppressive tumors. Type III interferons were believed to play overlapping roles with type I IFNs because they share a similar signaling pathway and induce similar transcriptional programs. However, type III IFNs are unique in their cell specific receptor expression and their antitumor activity is specific to a narrow range of cell types. Thus, type III IFN based therapies may show reduced toxic side effects compared with type I IFN based treatment. In this review, we focus on the development of IFN-based therapeutics used to treat different tumors. We highlight how the development in cytokine engineering has allowed for efficient delivery of type I and type III IFNs to tumor sites and look ahead to the obstacles that are still associated with IFN-based therapies before they can be fully and safely integrated into clinical settings.