USP18 and cancer: Many of these proteins are ISGs, and a number of them are part of a signature of genes that are upregulated in a subset of tumour cells, independent of immune infiltration.5 ISG-positive cancer cells are sensitive to ADAR loss, another ISG with deaminase activity, controlling the levels of dsRNA, an innate ligand.5,46 We identified USP18-dependent ISG15ylation of seven lysine residues in ADAR (K433, K637, K763, K781, K798, K895 and K996), localised within the dsRNA binding (dsRBD) and deaminase domains (DD), which may potentially affect both enzymatic activity and substrate binding affinity.