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.


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-γ and TNF-α 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-γ and TNF-α. 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.
Mirjačić Martinović
Katarina
K
Institute of Oncology and Radiology of Serbia, Belgrade, Serbia. kmirjacic@sezam.net
Konjević
Gordana
G
Babović
Nada
N
Inić
Momčilo
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D054343:Receptors, KIR2DL2 / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
D017252:CD3 Complex; D019002:CD56 Antigen; C515077:KIR2DL2 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C522918:NCAM1 protein, human; D054343:Receptors, KIR2DL2; D055607:Receptors, Natural Killer Cell