Single cell analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer

Abstract

Abstract A comprehensive investigation of ovarian cancer development at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnosis and treatments. In this study, we examined over half a million single-cell transcriptome data of 84 ovarian tumor patients across all clinical stages. Through integrative analysis, we identified heterogeneous epithelial-immune-stromal cellular compartments and their interactions in ovarian cancers. The epithelial cells displayed clinical subtype features with functional variance. Notably, we observed a significant increase in distinct T cell subtypes, including Tregs and CD8 + exhausted T cells after stage IC2. Additionally, we discovered antigen-presenting cancer-associated fibroblasts (CAFs), with myofibroblastic CAFs (myCAFs) exhibiting enriched extracellular matrix (ECM) functionality linked to tumor progression at stage IC2. We identified the NECTIN2-TIGIT ligand-receptor pair mediating T cell communication with epithelial, fibroblast, endothelial and other cell types. These findings shed light on the cellular compartments and functional aspects of ovarian cancer, providing insights into the molecular mechanisms underlying stage IC2 and potential therapeutic strategies for the disease.