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ABSTRACT
Introduction: Interferons (IFNs) play a key role in modulating anti-microbial and antitumor immune responses. In oncology, past attempts to exploit IFNs therapeutically did not fulfill expectations, and had only modest clinical results, mostly limited to adjuvant melanoma treatment. The recent successes of immunotherapy in oncology have brought new attention to the potential of immune-modulatory agents like the IFNs.
Areas covered: The authors review the biological effects of IFN on melanoma and immune cells. Then, the authors summarize the clinical results of adjuvant and therapeutic IFN in melanoma, giving focus to possible prognostic factors and new on-going clinical trials.
Expert opinion: IFNs offer intriguing opportunities for synergism between conventional treatments and recently introduced molecular-targeted and immunotherapy approaches. However, the full comprehension of all IFN effects and their multiple biologic links is challenging. A strong commitment toward parallel translational research is needed to facilitate the interpretation of IFN’s expected and unexpected effects, guiding the rational design of informative clinical studies.
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Article highlights
The antitumor potential of type-I IFN is based on direct pro-apoptotic and antiproliferative effects, and on extrinsic activity mediated by activation of multiple cell types of the immune system (αβ and γδ T cells, B lymphocytes, NK and DCs) and inhibition of other negative elements (e.g. Tregs; MDSC).
In the past IFN showed modest clinical results, mostly limited to the adjuvant treatment of melanoma.
IFN offers opportunities of synergism with conventional treatments and the recently introduced molecular targeted and immunotherapy approaches.
The full comprehension of all IFN effects with their multiple biologic links in a clinical setting is yet not possible, considering the complex network of different cells involved and the biologic intrinsic variability found in every patient.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.