While further studies are clearly required to clarify the role of PARP9 and DTX3L in the IFN response, we speculate that differences in genetic manipulation of PARP9/DTX3L levels (overexpression, RNA interference, or CRISPR/Cas9 KO) or cell types (fibrosarcoma, macrophage, or retinal pigment epithelia) could account for these differences. Here, PARP9 is linked to fibrosarcoma.