Phenotypic Landscape of Programmed Death and TIGIT/CD155/DNAM-1 Pathways in NK Cells in Ovarian Cancer

Objectives: Ovarian cancer (OC) is the gynecological malignancy with the highest mortality rate. Preclinical studies have shown that dual blockade of immune checkpoint proteins (ICPs), such as PD-1 and TIGIT, may be beneficial for OC patients. Thus, the aim of this study was to evaluate the expression of PD-1, TIGIT, and DNAM-1 in NK cells in three OC environments—i.e., peripheral blood (PB), peritoneal fluid (PF), and tumor tissue (TT)—and their soluble forms in plasma and PF to explore their clinical significance. Methods: The expression of ICPs on NK cells was analyzed via flow cytometry. The concentrations of soluble forms of these ICPs were measured in plasma and PF via ELISA. The obtained results were correlated with the clinicopathological features of OC patients. Results: We observed an increased percentage of PD-1+ NK cells in tumor tissue (p < 0.05), as well as TIGIT+ (p < 0.001) and DNAM-1+ NK cells in PF of patients with OC (p < 0.05). Soluble PD-1 (sPD-1) concentration was higher in PF than in plasma (p < 0.0001) and higher in plasma of OC patients than in controls (p < 0.001), while soluble TIGIT (sTIGIT) levels were elevated in plasma of OC patients compared with controls (p < 0.05). NK cell phenotypic alterations were also associated with selected clinicopathological features of OC (i.e., FIGO disease advancement, tumor type according to Kurman and Shih, and grade). The percentage of NK cells in PF was positively associated with age (p < 0.01) and negatively associated with BMI (p < 0.05). Conclusions: OC is characterized by distinct compartment-specific patterns of PD-1, TIGIT, and DNAM-1 expression on NK cells, accompanied by altered soluble ICP profiles. These phenotypic patterns may help define the immune landscape of the ovarian cancer microenvironment.