Isoform antagonism is especially pronounced in the context of melanoma, as SIRT1 associates with chemokine-rich CD8+-high niches and reinforces responses to PD-1 blockade, while SIRT7 triggers the IRE1α–XBP1 stress pathway to upregulate PD-L1 and promote immune evasion (164, 165). Here, ERN1 is linked to melanoma.