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

ESDR442 - Deciphering fibroblast heterogeneity in human skin cancer

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.