237 Cancer-associated fibroblasts with distinct origins and functions establish a pro-tumorigenic environment in squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is a serious public health problem due to its high incidence and metastatic potential. It progresses from actinic keratosis (AK), precancerous lesion, or thein situcarcinoma Bowen's disease (BD). During this progression, malignant keratinocytes activate dermal fibroblasts into tumor-promoting cancer-associated (CAFs), whose origin emergence remain largely unknown. Here, we generated analyzed >115,000 single-cell transcriptomes healthy skin, BD cSCC. Our results reveal immunoregulatory matrix-remodeling CAF subtypes that could be traced pro-inflammatory mesenchymal fibroblasts, respectively. These CAFs are absent in AK, change their proportions along the cSCC continuum, interact with different types establish pro-tumorigenic microenvironment. Notably, these findings were cSCC-specific not recapitulated basal carcinomas. study provides novel insights functionalities of will highly beneficial for specific targeting