Journal Article

Antitumour actions of interferons: implications for cancer therapy

Rautela, Jai, Hertzog, Paul J., Parker, Belinda S.

2016

Overview

Key Points A thorough review of the literature on interferon (IFN) use in cancer, using breast cancer as a case study, with discussion of the few clinical studies with sufficient numbers and sufficiently robust design to draw any conclusions. The clinical successes of IFNs (in other cancers) are often in blood-borne cancers and/or the setting of low tumour burden. New understanding of the immune response to tumours and its regulation by the different types of IFN provides exciting opportunities for redesigning when and how IFNs can be used in the clinic. IFNs are produced by various cell types in the tumour microenvironment, where they can have direct effects on tumour cells or indirect effects via modulation of the immune response. Technology-driven improvements in measuring IFN responses via transcriptomics (and potentially proteomics) provides insights into the signal transduction pathways activated or inactivated during tumorigenesis. They also provide 'signatures' that can indicate the potential responsivity of patients to particular forms of therapy, including IFN. A telling example is the discovery that tumour-cell-derived, IRF7-driven, type I IFN activates the immune system to target the process of metastasis. This paves the way for the use of IFN therapy in an adjuvant setting. There are indications requiring further study that IFN may work well in combination with other immune-based therapies (for example, checkpoint inhibitors that target the programmed cell death protein PD1 or its ligand, PDL1) or hormonal therapies for which synergistic effects might be expected because components of partner pathways are themselves IFN regulated. Interferons (IFNs) activate and regulate antitumour immune responses. This Review discusses lessons that can be learnt from using type I IFNs in oncology and our current understanding of the interferome in modifying antitumour immune responses. The interferons (IFNs) are a family of cytokines that protect against disease by direct effects on target cells and by activating immune responses. The production and actions of IFNs are finely tuned to achieve maximal protection and avoid the potential toxicity associated with excessive responses. IFNs are back in the spotlight owing to mounting evidence that is reshaping how we can exploit this pathway therapeutically. As IFNs can be produced by, and act on, both tumour cells and immune cells, understanding this reciprocal interaction will enable the development of improved single-agent or combination therapies that exploit IFN pathways and new 'omics'-based biomarkers to indicate responsive patients.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/67/1059/2325 / 631/67/327 / 631/67/580 / Antineoplastic Agents - therapeutic use / Biomedicine / Cancer / Cancer Research / Care and treatment / Genetic aspects / Humans / Immune response / Interferon / Interferons - physiology / Interferons - therapeutic use / Neoplasms - etiology / Neoplasms - therapy / Patient outcomes / review-article