Interferon-α as Antiviral and Antitumor Vaccine Adjuvants: Mechanisms of Action and Response Signature

Interferon-alpha (IFN-alpha) are cytokines endowed with multiple biologic effects, including activities on cells of the immune system, which are important for inducing protective antiviral and antitumor responses. Studies in mouse models have been instrumental for understanding the immune adjuvant activity of these cytokines and some of their mechanisms of action. In particular, recent studies conducted on both mouse and human models suggest that IFN-alpha act as effective immune adjuvants for inducing antiviral and antitumor immunity and that the effects of IFN on the differentiation and activation of dendritic cells (DC) play an important role in the induction of protective responses. In spite of the long record of IFN-alpha clinical use, a few clinical trials have attempted to evaluate the efficacy of these cytokines used as vaccine adjuvants. Recently, studies on the IFN-alpha signature in cells from patients treated with IFN-alpha under different modalities and various clinical settings have provided important insights for understanding the in vivo mechanisms of the IFN immune adjuvant activity in humans and may contribute to the identification of molecular markers with a clinical response. These studies further support the interest of evaluating the clinical efficacy of IFN-alpha when used as a vaccine adjuvant and also suggest that the DC generated in vitro from monocytes in the presence of this cytokine can exhibit a special advantage for the development of effective therapeutic vaccination strategies in cancer patients.