Multi-Omics Analysis Reveals Role of Cancer-Associated Fibroblasts in Cutaneous Squamous Cell Carcinoma

This study explores the role of cancer-associated fibroblasts (CAFs) in cutaneous squamous cell carcinoma (CSCC) using multi-omics analysis, including single-cell RNA sequencing and spatial transcriptomics. Analyzing 169,421 cells from CSCC and healthy controls, researchers identified 10 major cell types and eight CAF subtypes, with iCAFs-PLA2G2A and iCAFs-CXCL2 showing opposing roles in tumor progression. The study highlights the significant role of CAFs, particularly those expressing MDK, in promoting tumor progression through enhanced cell migration and invasion, and emphasizes the importance of the MDK-ITGA6 interaction. Differences between HPV-positive and HPV-negative CSCC were noted, with fibroblast enrichment contributing to the tumor microenvironment and progression, suggesting new therapeutic targets.