Characterizing the tumor microenvironment of metastatic ovarian cancer by single-cell transcriptomics

Abstract

Understanding the cellular composition of the tumor microenvironment and the interactions of the cells is essential to the development of successful immunotherapies in cancer. We perform single-cell RNA sequencing (scRNA-seq) of 9,885 cells isolated from the omentum in 6 patients with ovarian cancer and identify 9 major cell types, including cancer, stromal, and immune cells. Transcriptional analysis of immune cells stratifies our patient samples into 2 groups: (1) high T cell infiltration (high T_inf) and (2) low T cell infiltration (low T_inf). TOX-expressing resident memory CD8⁺ T (CD8⁺ Trm) and granulysin-expressing CD4⁺ T cell clusters are enriched in the high T_inf group. Concurrently, we find unique plasmablast and plasma B cell clusters, and finally, NR1H2⁺IRF8⁺ and CD274⁺ macrophage clusters, suggesting an anti-tumor response in the high T_inf group. Our scRNA-seq study of metastatic tumor samples provides important insights in elucidating the immune response within ovarian tumors.

Keywords: human cancer; immune cells; metastasis; ovarian cancer; scRNA-seq; solid tumor; transcriptomics.