Characterizing the Tumor Microenvironment of Metastatic Ovarian Cancer by Single Cell Transcriptomics

Abstract

Epithelial ovarian cancer is a highly heterogenous, metastatic and lethal disease. The presence of CD8+ T cells within ovarian tumors is positively associated with overall patient survival. Determining if a patient has T cells that respond to immunotherapies, their characteristics and how they can be manipulated to target cancer cells is an area of intense investigation in cancer therapy. This study determines the cellular composition and the transcriptional state of immune cells in solid metastatic ovarian cancer tumor samples from patients using single cell RNA sequencing (scRNA-seq). Hierarchical clustering stratified our patient samples into 2 main groups: 1) a high T cell infiltration (high Tinf ) group and 2) a low T cell infiltration (low Tinf) group. To assess the immune response in these patient samples, we performed an unsupervised clustering of the T cell population in each group. The T cell population clustered into 4 and 3 subpopulations in the high Tinf and low Tinf group respectively. A granulysin-expressing T cell cluster was identified and unique to the High Tinf group. Interestingly, although both groups had resident memory CD8+ T (CD8+ Trm) cells, only the CD8+ Trm cells in the high Tinf group expressed TOX , a recently described transcription factor that confers longevity to T cells within immunosuppressive environments such as cancer. Along with TOX+ CD8+ Trm cells, we found a unique plasmablast cluster and an IRF8+ macrophage cluster unique to the high Tinf group. Our comprehensive scRNA-seq study provides important insights in elucidating the immune response within ovarian tumors.