Increased killer immunoglobulin‐like receptor expression and functional defects in natural killer cells in lung cancer

Abstract

SummaryFrequencies 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.