290 iCAFs are the major source of chemokines in skin cancer

Cancer-associated fibroblasts (CAFs) play a key role in disease progression and treatment outcome. We used single-cell transcriptomics, CNV analysis, andin situ stainings to elucidate the yet unresolved intra-tumoral CAF heterogeneity melanoma non-melanoma skin cancer (basal squamous cell carcinoma, BCC SCC). identified three major subtypes, with their presence being indicative for tumor malignancy. RGS5+CAFs, which share features pericytes myofibroblasts, are conserved across all cancers. Matrix CAFs (mCAFs) ensheathing nests displaying highly increased extracellular-matrix gene expression, immuno (iCAFs) showing characteristic expression of proinflammatory immunomodulatory factors, cancer-type specific correlate differentiation status tumor-subtypes. Intriguingly, iCAFs an exclusive source chemokines within TME detected clusters aggressive SCC melanoma. Furthermore, conditioned medium from lines transforms normal into expressing high levels cytokines. Thus, we uncovered unique molecular programs driving either T-cell marginalization or immune recruitment surveillance, whose targeting might affect response immunotherapy.