title: Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.
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 CD56dimand CD56brightNK cells among the peripheral blood mononuclear cells (PBMCs) 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 CD56dimNK cells, whereas the baseline levels of CD56brightNK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56dimand CD56brightNK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56dimNK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56brightNK 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 NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56dimNK cells as well as normal baseline levels of CD56brightNK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56dimNK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56brightNK 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 CD56dimand CD56brightNK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab.
authors.affiliation: Department of Dermatology and Allergy, Munich University Hospital (LMU), Munich, Germany.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Tietze
authors.affiliation: Department of Dermatology and Allergy, Munich University Hospital (LMU), Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Angelova
authors.affiliation: Department of Dermatology and Allergy, Munich University Hospital (LMU), Munich, Germany.
authors.forename: Markus V
authors.initials: MV
authors.lastname: Heppt
authors.affiliation: Department of Dermatology and Allergy, Munich University Hospital (LMU), Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.affiliation: Department of Dermatology and Allergy, Munich University Hospital (LMU), Munich, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Berking
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D019002:CD56 Antigen / Q000378:metabolism; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D000074324:Ipilimumab / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D054398:Receptors, CCR4 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; C515354:CCR4 protein, human; C515370:CCR7 protein, human; D019002:CD56 Antigen; D006684:HLA-DR Antigens; D000074324:Ipilimumab; C522918:NCAM1 protein, human; D054398:Receptors, CCR4; D054400:Receptors, CCR7; C582435:pembrolizumab
keywords: CD56bright NK cells; CD56dim NK cells; NK cells; immune checkpoint blockade; response; survival