Immunogenomic profiles associated with response to immunotherapy in adolescent and young adult patients with melanoma

Adolescent and young adults (AYA) with advanced melanoma have unique immunogenic and clinical features that have not been fully explored in the context of their responsiveness to immune checkpoint blockade (ICB). In general, AYA tumours are poorly immunogenic and less responsive to ICB. In this study, we identified two subtypes of nonresponsive tumours that distinct in both the microenvironmental mechanism and location of regulatory T cells in AYA tumours when compared to adults. We observed that the enrichment of regulatory T cells in the peritumoural space and suppressed regulatory roles of cytokine receptors and their receptors are key factors of reduced ICB response in AYA patients, and these are distinct from those observed in older adults. We established a new immunosuppressive signature score, which we propose as a model for predicting ICB outcomes and finding combination strategies targeting the individual subtypes of AYA tumours.