IFN-I signaling in cancer: the connection with dysregulated Insulin/IGF axis.

Veronica Vella, Ernestina Marianna De Francesco, Eduardo Bonavita, Rosamaria Lappano, Antonino Belfiore

Journal: Trends in endocrinology and metabolism: TEM 2022;33(8):569-586

PMID: 35691786

Full Text on Elsevier Science View on PubMed

Abstract

Type I interferons (IFN-Is) are prototypical inflammatory cytokines produced in response to stress. IFN-Is have a critical role in antitumor immunity by driving the activation of leukocytes and favoring the elimination of malignant cells. However, IFN-I signaling in cancer, specifically in the tumor microenvironment (TME), can have opposing roles. Sustained IFN-I stimulation can promote immune exhaustion or enable tumor cell-intrinsic malignant features. Herein, we discuss the potential impact of the insulin/insulin-like growth factor system (I/IGFs) and of metabolic disorders in aberrant IFN-I signaling in cancer. We consider the possibility that targeting I/IGFs, especially in patients with cancer affected by metabolic disorders, contributes to an effective strategy to inhibit deleterious IFN-I signaling, thereby restoring sensitivity to various cancer therapies, including immunotherapy.

Address: Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, 95122 Catania, Italy.; IRCCS Humanitas Research Hospital, Fondazione Humanitas per la Ricerca, Laboratory of Cellular and Molecular Oncoimmunology, 20089 Rozzano, Italy; Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, UK.; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.; Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, 95122 Catania, Italy. Electronic address: [email protected].

DOI: 10.1016/j.tem.2022.04.009

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MeSH Terms: Humans, Insulin, Insulin-Like Growth Factor I, Neoplasms, Signal Transduction, Tumor Microenvironment