Analyses of peripheral blood NK cells in response to anti-PD-1 therapy in metastatic melanoma patients

Therapeutical blockade of programmed cell death protein 1 (PD-1) axis may enhance anti-tumor immunity and especially natural killer (NK) cells activity. In 32 BRAF wild type (wt) metastatic melanoma (MM) patients before and after every 12 weeks of therapy with PD-1 inhibitor, Pembrolizumab, we analyzed the percentage of T cell subsets, NK cells and CD14⁺HLA-DR⁻ monocytes, the expression of CD107a degranulation marker, activating NKG2D, NKp46, DNAM-1 and inhibitory CD158a receptors on NK cells by Flow cytometry, until one year or disease progression (DP). The patients with disease control (non-DP patients) had significant increase in lymphocyte count, percentage of NK cells, increased expression of CD107a, NKG2D, NKp46, but decreased CD158a on NK cells during Pembrolizumab therapy compared to pretherapy values. Patients with DP had increased neutrophil number, increased percentage of immunosuppressive CD14⁺HLA-DR⁻ monocytes, as well as increased CD158a expression on NK cells. In MM patients with disease control, contrary to DP patients blocking of PD-1 inhibitory molecule may increase NK cell cytotoxicity through enhancement of NK cell degranulation and activating receptor expression. Therefore, our findings show that NK cells and their receptors in MM patients may be potential biomarkers of response to Pembrolizumab.