442 Deciphering fibroblast heterogeneity in human skin cancer

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and play an important role in disease progression treatment outcome. Here we used single-cell transcriptomics, CNV analysis, situ stainings to elucidate yet unresolved intra-tumoral CAF heterogeneity melanoma, basal squamous cell carcinoma. We identified three major subtypes, with their presence being indicative for malignancy. RGS5+ CAFs, which share features pericytes, present all tumors. Immuno CAFs (iCAFs) showing characteristic expression proinflammatory immunomodulatory factors, matrix (mCAFs) displaying highly increased extracellular-matrix gene expression, cancer-type specific correlate differentiation status tumor-subtypes. This study also reveals dramatic influence tumor-microenvironment on transcriptome non-malignant cells within tumors neoplasm-free adjacent skin, highlights tremendous differences genomic aberrations histologically indistinguishable cancer-subtypes. skin cancer atlas detailed portray diversity, may advance future diagnostic strategies open new avenues better personalized therapies.