Characterization of Natural Killer and Innate Lymphoid Cell Immunity in Ovarian Cancer and Endometriosis

Abstract

Ovarian cancer (OC) is the most lethal gynecological cancer, due to discovery at late stages, vague symptoms and yet no effective screening methods. A common side effect of OC is the buildup of peritoneal fluid or ascites, which contain a large number of immune cells and tumor cells and spheroids. Moreover the carcinoma is heterogeneous and includes various types of tumors with distinctly varying molecular pathways. Endometriosis is a common benign inflammatory disease and is highly associated with certain subtypes of ovarian cancers, including endometrioid and clear cell OC. However, the mechanism behind the transition from endometriosis to OC is not fully understood, but previous research suggests genetic mutations associated with immune escape might play a role. This project explores the immune landscape in high grade ovarian cancer, with emphasis on phenotypes of natural killer (NK) cells and innate lymphoid cells (ILCs) in ascites and matched peripheral blood mononuclear cells (PBMCs). Using spectral flow cytometry with clustering and dimensionality reduction, distinct immune cell populations were identified. Two populations were found that were significantly enriched in ascites, including one clear population of NK cells with clear tissue resident properties recognized by high expression of markers CD49a, CD103 and CD69 as well as of NK cell receptors, including NKG2A which aligns with previous results in the research group. In parallel, six NK cell receptor-related SNPs were analyzed using public GWAS datasets for endometriosis and endometrioid and clear cell OC. The results showed slight significance for SNPs in genes associated with the NK cell receptors NKG2A, NKp30, and HLA-B-21. These results may have relevance in the susceptibility for ovarian cancer and impaired NK cell regulation in endometriosis and ovarian cancer highly associated with endometriosis. These findings further deepened the understanding of variances in immunity in ovarian cancer and endometriosis and could in the future potentially identify immunotherapeutic targets in tissue resident populations in ascites fluid.