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.

I 型干扰素 (IFN-Is) 是响应压力而产生的典型炎性细胞因子。IFN-Is通过驱动白细胞的活化和有利于消除恶性细胞在抗肿瘤免疫中起关键作用。然而，癌症中的 IFN-I 信号传导，特别是在肿瘤微环境 (TME) 中，可能具有相反的作用。持续的 IFN-I 刺激可以促进免疫衰竭或使肿瘤细胞固有的恶性特征成为可能。在这里，我们讨论了胰岛素/胰岛素样生长因子系统 (I/IGF) 和代谢紊乱对癌症中异常 IFN-I 信号传导的潜在影响。我们认为靶向 I/IGFs 的可能性，特别是在患有代谢紊乱的癌症患者中，有助于抑制有害 IFN-I 信号传导的有效策略，