USP18 and cancer: This pathway is triggered by a variety of stress- and inflammation-related signals within the TME (e.g., hypoxia [283], proinflammatory cytokines [284], and VEGF [285]) and leads to tumor progression and immune suppression by altering the expression of the ISGs IFIT2, IRF7, MX2, and USP18 in cancer cells and of IL-2 in immune cells [150,276]; (ii) impairment of IFNAR1 signaling through SOCS-mediated prevention of STAT1 phosphorylation [286]; (iii) silencing or loss-of-function mutations of JAKs and STATs [157,270,287,288]; and (iv) downregulation of IRFs [289,290,291].