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. How-ever, 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, includ-ing immunotherapy.

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

Vella, Veronica
Co-primo
;
De Francesco, Ernestina Marianna
Co-primo
;
Belfiore, Antonino
2022

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. How-ever, 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, includ-ing immunotherapy.
IGF axis
insulin receptor isoform A
insulin receptor isoforms
interferon signaling
Humans
Insulin-Like Growth Factor I
Signal Transduction
Tumor Microenvironment
Insulin
Neoplasms
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/541372
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