The Stage Dependent Changes in NK Cell Activity and the Expression of Activating and Inhibitory NK Cell Receptors in Melanoma Patients

Background. As NK cell antitumor activity is regulated by the balance between numerous activating and inhibitory receptors the aim of this study was to analyze the changes in these receptors expression as well as the differences in their association with NK cell activity in melanoma patients in different clinical stages. Materials and Methods. Forty-three melanoma patients in the three different clinical stages and 17 healthy controls were analyzed for NK cell activity by the standard (51)Cr radioactive assay, as well as for the percentage and absolute number of CD3-CD56+ NK cells and their subsets and the expression of degranulation marker CD107a, activating NKG2D and CD161, and inhibitory KIR, CD158a, and CD158b receptors on CD3-CD56+ NK cells by flow cytometry. IFN-gamma and TNF-alpha PBL production were evaluated by enzyme-linked immunosorbent assay (ELISA). Results. We show that contrary to nonmetastatic, metastatic melanoma patients have significantly impaired NK cell activity, lower CD107a expression, as well as decreased production of IFN-gamma and TNF-alpha. Furthermore, these melanoma patients have a significant decrease in the expression of activating NKG2D receptor, which positively correlates with NK cytotoxicity, and a significant increase in the expression of inhibitory CD158b on CD3-CD56+ NK cells compared with healthy controls. Conclusions. In this study, we show that metastatic melanoma patients have significant changes in NK cell activity and the expression of activating as well as inhibitory NK cell receptors. These results indicate that only in this patient group, the blocking of inhibitory or enhancing of activating NK cell receptor expression may promote NK cell-mediated cytolysis. (C) 2011 Elsevier Inc. All rights reserved.