Interferon α in cancer immunoediting: From elimination to escape

Interferon alpha (IFN alpha) is a cytokine that mediates diverse immune responses to tumours. It is the oldest immune-based oncologic drug and has been widely used to treat various malignancies in humans. Yet, the use of IFN alpha in cancer therapy has only resulted in limited success and even led to worse clinical outcomes under certain instances. The emergence of the cancer immunoediting concept-which implicates the host immune system in promoting tumour growth-recapitulates the need to evaluate the immune functions of IFN alpha. This review proposes that IFN alpha has dual opposing roles in cancer development based on the mutational status of its signalling components, which determines the expression of anti- or pro-tumorigenic IFN-stimulated genes (ISGs). This duality may translate into new applications of IFN alpha in cancer immunotherapy.