title: Increased killer immunoglobulin-like receptor expression and functional defects in natural killer cells in lung cancer.
abstract: Frequencies of natural killer (NK) cells from patients with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) did not differ from healthy controls. A higher proportion of NK cells from NSCLC patients expressed the killer immunoglobulin-like receptor (KIR) CD158b than in controls (P = 0.0004), in the presence or absence of its ligand, HLA-C1. A similar result was obtained for CD158e in the presence of its ligand HLA-Bw4 in NSCLC patients (P = 0.003); this was entirely attributable to the Bw4I group of alleles in the presence of which a fivefold higher percentage of CD158e(+) NK cells was found in NSCLC patients than controls. Proportions of CD158b(+) NK cells declined with advancing disease in NSCLC patients. Expression of NKp46, CD25 and perforin A, and production of interferon-γ following stimulation with interleukin-12 and interleukin-18, were all significantly lower in NK cells from NSCLC patients than in controls. Both NK cell cytotoxicity and granzyme B expression were also reduced in lung cancer patients. Increased inhibitory KIR expression would decrease NK cell cytotoxic function against tumour cells retaining class I HLA expression. Furthermore, the reduced ability to produce interferon-γ would restrict the ability of NK cells to stimulate T-cell responses in patients with lung cancer.
authors.affiliation: Department of Clinical Infection, Microbiology & Immunology, Institute of Global Health, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK.
authors.forename: Suliman Y
authors.initials: SY
authors.lastname: Al Omar
authors.forename: Ernie
authors.initials: E
authors.lastname: Marshall
authors.forename: Derek
authors.initials: D
authors.lastname: Middleton
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Christmas
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D002469:Cell Separation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D054340:Receptors, KIR / Q000096:biosynthesis; D054344:Receptors, KIR2DL3 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3