Interferon: current status and future prospects in cancer therapy

Type I interferons (IFNs) exhibit antiproliferative activity and apoptotic effects, and regulate an immune response by activating multiple cells types, including dendritic cells, cytotoxic T cells, and natural killer cells. Most recently, a report in the literature identified dysfunctional induction of a type I IFN response in cancer stem cells--specifically, breast cancer-initiating cells, implicating this defect in progression to breast cancer. Indeed, accumulating evidence suggests that cancer stem cells/cancer-initiating cells are prevalent in leukemias and solid tumors, are resistant to chemotherapy and radiation therapy, and therefore likely contribute to tumor recurrence. IFN-β treatment of human glioma xenografts leads to disruption of the vascular niche of glioma stem cells, in further support of a potential therapeutic effect of IFN treatment in limiting cancer stem cells. The implications are that restoring an IFN response, or enhancing an IFN response, may invoke a reduction, or elimination of both cancer stem cells and tumor cells. In this review, the clinical application of type I IFNs, mainly IFN-αs, will be reviewed.