Type I interferons: History and perspectives as immunotherapeutic agents against cancer

Abstract

Interferons (IFNs) were first described in the context of viral infection as macromolecules capable of interfering with the ability of a viral particle to infect a host cell. Besides viral interference, since their discovery, IFNs have been further implicated in different processes linked to immunity and cancer. The family of IFNs has been divided into three categories according to biological properties and signaling pathways: type I IFNs (consisting of IFN-α and β), type II IFNs (IFN-γ, also known as the immune IFN), and type III IFNs (consisting of IFN-λ). This chapter focuses on type I IFNs, which are closely linked to key processes in cancer, such as malignant transformation, differentiation, tumor cell growth, and death. Within the immune system, type I IFNs communicate with several populations involved in the antitumor immune response, such as NK (natural killer) and dendritic cells, contributing to cancer immunoediting. Type I IFNs are approved for the treatment of a number of cancers, including melanoma, renal cell carcinoma, and Kaposi's sarcoma. However, currently the biggest challenge in the therapeutic use of type I IFNs, as well as other cytokines, is the toxic side effects, which can compromise the efficacy of the treatment and reduce patient's quality of life. In this chapter, we review the biology of type I IFNs along with many therapeutic approaches being currently explored in order to reduce toxicity and fully harness the antitumor potential of type I IFNs.