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

Immunology. 2011 May;133(1):94-104. doi: 10.1111/j.1365-2567.2011.03415.x. Epub 2011 Feb 22.


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.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Separation
  • Cytokines / immunology
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / immunology*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / immunology*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Receptors, KIR / biosynthesis
  • Receptors, KIR2DL3 / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Cytokines
  • Receptors, KIR
  • Receptors, KIR2DL3