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Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy
Author(s) -
Tietze Julia K.,
Angelova Daniela,
Heppt Markus V.,
Ruzicka Thomas,
Berking Carola
Publication year - 2017
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13263
Subject(s) - ipilimumab , melanoma , medicine , baseline (sea) , metastatic melanoma , immunology , immunotherapy , oncology , cancer research , immune system , biology , fishery
Abstract The introduction of immune checkpoint blockade ( ICB ) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T‐cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD 56 dim and CD 56 bright NK cells among the peripheral blood mononuclear cells ( PBMC 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 NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD 56 dim NK cells, whereas the baseline levels of CD 56 bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD 56 dim and CD 56 bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD 56 dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD 56 bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG 2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD 56 dim NK cells as well as normal baseline levels of CD 56 bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD 56 dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD 56 bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD 56 dim and CD 56 bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab.