Biomarkers of suppressed natural killer (NK) cell function in metastatic melanoma: decreased NKG2D and increased CD158a receptors on CD3-CD16+ NK cells.

In metastatic melanoma (MM) patients we evaluated natural killer (NK)-cell activity, distribution of several NK receptors and their correlation with NK function. Peripheral blood lymphocytes (PBL) of MM patients and controls were analysed for NK activity and expression of activating NKG2D, CD161 and KIR, CD158a and CD158b receptors on CD3-CD16+ NK cells. MM patients not only had significantly decreased NK activity and NK-cell interferon (IFN)-gamma production, a redistribution of NK-cell subsets with an increase in CD16(dim) and a reduction in CD16(bright) NK subsets. There was a decreased CD161 and NKG2D and an increased CD158a NK-cell expression in MM patients, with a positive correlation between NKG2D expression and NK cytotoxicity and an inverse correlation between CD158b expression and NK-cell cytotoxicity in patients. Furthermore, patients' CD3-CD16(bright) NK subset showed lower expression of CD161 and CD158a. Therefore, NKG2D, CD158a and CD158b expression in MM patients may represent several clinically useful 'biomarkers' of suppressed NK function.