title: Expansion of CD16-negative natural killer cells in the peripheral blood of patients with metastatic melanoma.
abstract: Altered natural killer (NK) cell function is a component of the global immune dysregulation that occurs in advanced malignancies. Another condition associated with altered NK homeostasis is normal pregnancy, where robust infiltration with CD16- CD9+ NK cells can be identified in decidual tissues, along with a concomitant expansion of CD16- NK cells in the maternal peripheral blood. In metastatic melanoma, we identified a similar expansion of peripheral blood CD16- NK cells (median 7.4% in 41 patients with melanoma compared with 3.0% in 29 controls, P < .001). A subset of NK cells in melanoma patients also expresses CD9, which is characteristically expressed only on NK cells within the female reproductive tract. Expansion of CD16- NK cells was associated with elevated plasma transforming growth factor-beta (TGF-β levels (median 20  ng/ml, Spearman's ρ = 0.81, P = .015)). These findings suggest the possibility of exploring anti-TGF-β therapy to restore NK function in melanoma.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic Graduate School of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Shernan G
authors.initials: SG
authors.lastname: Holtan
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Creedon
authors.forename: Michael A
authors.initials: MA
authors.lastname: Thompson
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Nevala
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
mesh_terms: D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D009362:Neoplasm Metastasis; D011247:Pregnancy; D017452:Receptors, IgG / Q000172:deficiency / Q000276:immunology; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D060245:Tetraspanin 29; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000276:immunology
chemical_list: D015703:Antigens, CD; C554869:CD9 protein, human; C496124:FCGR3A protein, human; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D060245:Tetraspanin 29; D016212:Transforming Growth Factor beta