Role of cellular metabolism in regulating type I interferon responses: Implications for tumour immunology and treatment. (28th November 2017)

• Record Type: Journal Article
• Authors: Ahmed, Duale; Cassol, Edana
• Is Part Of: Cancer letters. Volume 409(2017)
• Page Start: 20
• Page End: 29
• Publication Date: 2017-11-28
• Subjects: Type I interferons -- Immunometabolism -- Antiviral immune responses -- Inflammation -- Cancer; IFN interferon -- ISG interferon stimulated genes -- PD-L1 program death-ligand 1 -- TLR Toll-like receptor -- RIG retinoic acid-inducible gene-like helicases -- RLR RIG-I-like receptor -- PAMP pathogen-associated molecular pattern molecule -- DAMP damage-associated molecular pattern molecule -- IFNAR IFN-α receptor -- IRF IFN regulatory factor -- ISGF3 IFN-stimulated gene factor -- ISRE IFN-stimulated response elements -- PI3K phosphatidylinositol 3-kinase -- NF-κB nuclear factor-κB -- mTOR mammalian target of rapamycin -- PIKK PI3K-related kinase -- PGC-1α PPARG coactivator-1α -- ETC electron transport chain -- mTORC mTOR complex -- FAO fatty acid oxidation -- OXPHOS oxidative phosphorylation -- TCA tricarboxylic acid -- BMM mouse bone marrow-derived macrophages -- PFKFB3 6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase -- RSV respiratory syncytial virus -- DC dendritic cell -- HIV human immunodeficiency virus -- SLE systemic lupus erythematosus -- RRMS relapsing-remitting multiple sclerosis -- HCMV human cytomegalovirus -- FA fatty acid -- SREBP sterol regulatory element-binding protein -- SCAP SREBP cleavage-activating protein -- MAS meiosis-activating sterols -- 25-HC 25-hydroxycholesterol -- LXR liver X receptor -- SOCS Suppressor of cytokine signaling -- IDO1 Indoleamine 2, 3-dioxygenase 1 -- NOS nitric oxide synthase -- ADC arginine decarboxylase -- AGAT arginine:glycine amidinotransferase -- NO nitric oxide; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.08.037
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Type I interferons (IFN) are increasingly recognized for their role in regulating anti-tumour immune responses. However, chronic activation of these pathways can result in immunosuppression and has been linked to poor responses to genotoxic and radiotoxic therapies. Emerging evidence suggests energy, lipid and amino acid metabolism play an important role in regulating and fine tuning type I IFN responses. Further, dysregulation of these processes has been implicated in the pathogenesis of chronic viral infections and autoimmune disorders. Systematic evaluation of these interrelationships in cancer models and patients may have important implications for the development of targeted IFN based anti-cancer therapeutics with minimal toxicity and limited off target effects. Highlights: Type I IFN responses are regulated by energy, lipid and amino acid metabolism. Dysregulation of metabolism contributes to pathogenesis of infections and autoimmune disorders. Altered metabolism may contribute to dichotomous role of type I IFNs in tumour immunology. Regulation of metabolic processes may improve the efficacy of IFN based anti-cancer therapeutics.