Phenotyping of immune and endometrial epithelial cells in endometrial carcinomas revealed by single-cell RNA sequencing

Abstract

Tumors are complex ecosystems harboring multiple cell types which might play a critical role in tumor progression and treatment response. The endometrial epithelial cell identities and immune microenvironment of endometrial carcinoma (ECC) are poorly characterized. In this study, a cellular map of endometrial carcinoma was generated by profiling 30,780 cells isolated from tumor and paratumor tissues from five patients using single-cell RNA sequencing. 7 cell types in lymphocytes, 7 types in myeloid cells and 3 types in endometrial epithelial cells were identified. Distinct CD8⁺ T cell states and different monocyte-macrophage populations were discovered, among which exhausted CD8⁺ T cells and macrophages were preferentially enriched in tumor. Both CD8⁺ T cells and macrophages comport with continuous activation model. Gene expression patterns examination and gene ontology enrichment analysis of endometrial epithelial cells revealed 3 subtypes: stem-like cells, secretory glandular cells and ciliated cells. Overall, our study presents a view of endometrial carcinoma at single-cell resolution that reveals the characteristics of endometrial epithelial cells in the endometrium, and provides a cellular landscape of the tumor immune microenvironment.