Additionally, the RNA editing enzyme ADAR1 has long been known to be a major repressor of Z-type dsRNA (a substrate of ZBP1), and this suppression mechanism results in resistance and poor reactivity to ICIs, while the use of small-molecule drug, CBL0137, directly induces Z-type dsDNA formation in cells and results in activation of ZBP1-depenent necroptosis, which significantly reverses ICIs unresponsiveness of melanoma mouse models [236]. Here, ZBP1 is linked to melanoma.