Baseline immunosuppressive spatiotypes in adolescent and young adult melanoma patients treated with checkpoint immunotherapy

We compared the transcriptomic, genomic, and spatial cellular profiles of the tumor microenvironment (TME) in AYA and adult melanomas to determine the pathways associated with ICI outcomes in AYA patients. We identified two ICI-resistant spatiotypes of AYA melanoma with distinct stroma infiltrating lymphocytes (SILs) unique from adult TME; SILhigh subtype was enriched for regulatory T-cells in the peritumoral space and showed alternative checkpoint expression (e.g. TIM3, ICOS), while the SILlow subtype showed a lack of immune induction. We further established a novel YIM (young immunosuppressive melanoma) score for predicting ICI response for AYA patients and proposed personalized therapeutic strategies for the ICI-resistant subgroups.