IFNA1 and neoplasm: However, persistent ISG hubs in tumors, as shown in a recent MMRd CRC tumor atlas (47), may ultimately drive immunosuppression because of the negative feedback that upregulates immune checkpoints and co-inhibitory factors such as PD1/PDL1, Lag3/MHC-II, Tim3/LGALS9, and IDO1 through IFN overstimulation (47) (Figure 3D).