title: Preferential apoptosis of CD56dim natural killer cell subset in patients with cancer.
abstract: Natural killer (NK) cells (CD56(+)/CD3(-)) in the circulation of cancer patients were reported to have low NK activity and undergo spontaneous apoptosis. A possible relationship between apoptosis and impaired NK activity was studied by Annexin V-binding and NK-cell assays performed with peripheral blood mononuclear cells of patients with head and neck cancer (HNC), breast cancer (BC) and normal controls (NC). Cells stained with Annexin V (Anx) and antibodies to CD56, CD3, CD95, CD25, CD122 or CD132 were examined by flow cytometry. NK activity was tested against K562 targets in 4-h (51)Cr-release assays. The ratio of CD56(dim)/CD56(bright) NK cells was significantly different in patients vs. controls (10 vs. 16; p<0.01). A significantly greater percentage of CD56(dim) NK cells bound Anx in HNC patients (27+/-17%, median +/- SD) or BC (46+/-18%) than in NC (15+/-18%, p<0.04 and p<0.0002, respectively). CD56(dim) NK cells were preferentially targeted for apoptosis. NK activity was significantly lower in patients with HNC and BC than in NC (p<0.009). An inverse correlation between NK activity and the percent of Anx(+)CD56(dim) NK cells was observed in cancer patients (p =0.002) but not in NC. In patients, circulating CD56(dim) NK cells were targeted for apoptosis, leading to low levels of NK activity.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauernhofer
authors.forename: Iris
authors.initials: I
authors.lastname: Kuss
authors.forename: Brent
authors.initials: B
authors.lastname: Henderson
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Baum
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D019002:CD56 Antigen / Q000378:metabolism*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D011485:Protein Binding; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D017304:Annexin A5; D019002:CD56 Antigen; D015375:Receptors, Interleukin-2