025 Transcriptional profiling of cutaneous immunotoxicity from melanoma immunotherapy

Immunotherapy has drastically improved the survival prospect for advanced melanoma. Unfortunately, these treatments often come with cutaneous side effects which may cause patient to discontinue or delay therapy. To understand mechanism of immunotoxicity in relation clinical presentation, we characterized symptom clusters by and histologic morphology, severity rating, transcriptional analyses patients before, during, after immunotherapy. As 2020, 30 subjects were recruited, 12 developed rashes (83% eczematous, 17% psoriasiform) who treated only topical steroids. Histologically, 75% demonstrated spongiotic dermatitis; 42% a purely lymphocytic infiltrate while 8% primarily eosinophilic. Quality life (QoL) was impacted rash, as score increase on Skindex, ItchyQoL ItchyQuant. We next extracted RNA from FFPE punch biopsies assess differences between baseline prior therapy, corresponding normal rash tissues during Transcriptional at different subtypes not significant, defined 2-fold change FDR<0.05. However, lesions compared tissues, 3140 1287 genes, mainly immune-related such T cell receptor signaling molecules, co-stimulatory receptors, cytotoxic effector chemokine upregulated, 1522 934 genes mostly tight junctional adhesion molecules lipid syntheses downregulated. GSEA revealed that samples reflected signatures similar memory CD8 cells found vaccination, PD-1 signaling, allograft rejection, various cytokine pathways. In conclusion, is mediated pro-inflammatory processes downregulation junctions syntheses, clinically manifests impact QoL.