Description:
<jats:title>Abstract</jats:title><jats:p>The introduction of immune checkpoint blockade (<jats:styled-content style="fixed-case">ICB</jats:styled-content>) has been a breakthrough in the therapy of metastatic melanoma. The influence of <jats:styled-content style="fixed-case">ICB</jats:styled-content> on T‐cell populations has been studied extensively, but little is known about the effect on <jats:styled-content style="fixed-case">NK</jats:styled-content> cells. In this study, we analysed the relative and absolute amounts of <jats:styled-content style="fixed-case">NK</jats:styled-content> cells and of the subpopulations of <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>dim</jats:sup> and <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>bright</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells among the peripheral blood mononuclear cells (<jats:styled-content style="fixed-case">PBMC</jats:styled-content>s) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of <jats:styled-content style="fixed-case">NK</jats:styled-content> cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>dim</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells, whereas the baseline levels of <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>bright</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells were either normal or abnormally high. The relative and absolute amounts of <jats:styled-content style="fixed-case">NK</jats:styled-content> cells and of <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>dim</jats:sup> and <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>bright</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of <jats:styled-content style="fixed-case">NK</jats:styled-content> cells and <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>dim</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>bright</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells was unaffected by treatment. The baseline levels of <jats:styled-content style="fixed-case">NK</jats:styled-content> cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of <jats:styled-content style="fixed-case">NKG</jats:styled-content>2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of <jats:styled-content style="fixed-case">NK</jats:styled-content> cells and <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>dim</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells as well as normal baseline levels of <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>bright</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>dim</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>bright</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total <jats:styled-content style="fixed-case">NK</jats:styled-content> cells and of <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>dim</jats:sup> and <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>bright</jats:sup> <jats:styled-content style="fixed-case">NK</jats:styled-content> cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab.</jats:p>