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

• Published in: Communications biology Vol. 7; no. 1; pp. 131 - 15
• Main Authors: Chai, Chaochao, Liang, Langchao, Mikkelsen, Nanna S., Wang, Wei, Zhao, Wandong, Sun, Chengcheng, Bak, Rasmus O., Li, Hanbo, Lin, Lin, Wang, Fei, Luo, Yonglun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/109; 42; 42/41; 45; 45/44; 631/114/2164; 631/67/1517/1709; Biomedical and Life Sciences; CD8 antigen; Cell proliferation; CRISPR; Epithelial cells; Extracellular matrix; Life Sciences; Lymphocytes T; Molecular modelling; Ovarian cancer; Transcriptomes; Tumor microenvironment; Tumors
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-05826-1

A comprehensive investigation of ovarian cancer (OC) progression at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnoses and treatments. Here, over half a million single-cell transcriptome data were collected from 84 OC patients across all clinical stages. Through integrative analysis, we identified heterogeneous epithelial-immune-stromal cellular compartments and their interactions in the OC microenvironment. The epithelial cells displayed clinical subtype features with functional variance. A significant increase in distinct T cell subtypes was identified including Tregs and CD8+ exhausted T cells from 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. Furthermore, the NECTIN2-TIGIT ligand-receptor pair was identified to mediate T cells communicating with epithelial, fibroblast, endothelial, and other cell types. Knock-out of NECTIN2 using CRISPR/Cas9 inhibited ovarian cancer cell (SKOV3) proliferation, and increased T cell proliferation when co-cultured. These findings shed light on the cellular compartments and functional aspects of OC, providing insights into the molecular mechanisms underlying stage IC2 and potential therapeutic strategies for OC. A single-cell interaction study on ovarian cancer reveals heterogeneous epithelial-immune-stromal cellular compartments and their interactions in shaping the tumor microenvironment, especially through the NECTIN2-TIGIT interaction.