In the present study, we report the analysis of NK cells derived from patients suffering from a rare
ovarian cancer histotype of clear cell
carcinoma (OCCC) resistant to conventional
chemotherapies. We analyzed the phenotype of NK cells derived from peripheral blood (PB) and peritoneal fluid (PF) and evaluated cytotoxic interactions between NK cells and autologous
tumor cells (ATC) derived from patients. We provided evidence of impaired degranulation capacity of NK cells derived from patients' PF in the presence of ATC. Analyzing
tumor cell
ligands recognized by
NK cell receptors, we found that ATC are characterized by an HLA class I+ phenotype (although the level of HLA-I expression varies among all patients) and by a heterogeneous expression of
ligands for activating NK receptors (from normal to decreased expression of some markers). Furthermore, we observed a down-regulation of crucial NK cell activating receptors, primarily
DNAX Accessory Molecule-1 (DNAM-1), on
tumor-associated NK cells. Based on these results, we propose that this severe lysis defect may be due to both negative interactions between HLA-I-specific inhibitory
NK cell receptors/HLA-I molecules and to defective interactions between activating NK receptors and cognate
ligands. In conclusion, for the first time, the phenotypic and functional properties of
tumor-associated NK cells and their ATC derived from PF of patients with advanced stage of OCCC were characterized. Taken together results indicate altered interactions between NK cells and ATC and shed light on the aggressive mechanisms of this
cancer histotype. Further studies on this rare
tumor will be helpful to improve and define more effective
therapies.