Decitabine induces innate immune gene expression in rare melanoma models

Rare melanoma subtypes, including mucosal melanoma, can exhibit reduced tumor-intrinsic innate immune and interferon-associated gene expression, which may contribute to immune evasion and limited responses to immune checkpoint inhibitors. We investigated whether decitabine, a DNA methyltransferase inhibitor known to induce viral mimicry and immune-associated transcriptional programs, could restore innate immune and interferon-associated signaling in rare melanomas. Here, we report RNA-seq profiling of the MB2141 anorectal mucosal melanoma model following decitabine treatment in vitro and in vivo. Decitabine treatment resulted in robust induction of innate immune pathogen sensing, type I interferon signaling, antigen presentation, and other immune-associated gene expression programs. These data provide a transcriptional framework for understanding how DNA hypomethylating agents modulate immune gene expression in mucosal melanoma and support further investigation of decitabine as an immune-priming strategy for rare melanoma subtypes.