Type I interferons in anticancer immunity View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-06-01

AUTHORS

Laurence Zitvogel, Lorenzo Galluzzi, Oliver Kepp, Mark J. Smyth, Guido Kroemer

ABSTRACT

Key PointsThe type I interferon (IFN) system involves a single form of IFNβ, several variants of IFNα and other less well-characterized IFNs, all of which signal via a heterodimeric IFNα/β receptor 1 (IFNAR1)–IFNAR2 receptor to transactivate IFN-stimulated genes (ISGs). IFNβ also promotes the transactivation of ISGs through homodimeric IFNAR1.The secretion of type I IFNs is stimulated by viral constituents, as well as by danger signals emitted by dying cells, including nuclear and mitochondrial nucleic acids found at ectopic locations. The production of type I IFNs has marked antiviral and immunostimulatory effects.Beyond their role in curtailing viral infection, type I IFNs play an essential part in natural cancer immunosurveillance, functioning both at the level of malignant cell precursors and through effects on the immune system. Thus, the knockout of Ifnar1 in mouse epithelial cells predisposes them to malignant transformation, as does the knockout of Ifnar1 in leukocytes, especially dendritic cells.Type I IFN signalling is also essential for the full-blown efficacy of various anticancer agents, including chemotherapeutics (such as anthracyclines), antibodies that target growth factor receptors (such as human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR)), the injection of adjuvants and oncolytic virotherapy.The expression levels of ISGs constitute a positive prognostic or predictive biomarker in patients affected by several cancers including melanoma and breast carcinoma. Recombinant type I IFNs have been successfully used for the treatment of various human neoplasms, particularly ulcerative melanoma, renal cell carcinoma and hepatitis B virus (HBV)-induced hepatocellular carcinoma.Preclinical data identify four distinct approaches to improve the targeted delivery of type I IFNs to malignant lesions: first, fusing or linking recombinant type I IFNs to antibodies specific for tumour-associated surface antigens; second, engineering leukocytes or mesenchymal stem cells to express type I IFNs once they have infiltrated neoplastic lesions; third, injecting type I IFN-encoding vectors into the tumour mass; and fourth, supplying artificial ligands of type I IFN-stimulating pattern recognition receptors (PRRs). More... »

PAGES

405-414

References to SciGraph publications

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  • Journal

    TITLE

    Nature Reviews Immunology

    ISSUE

    7

    VOLUME

    15

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nri3845

    DOI

    http://dx.doi.org/10.1038/nri3845

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1049369736

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26027717


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