Expansion of natural killer cells in patients with head and neck cancer: detection of "noninhibitory" (activating) killer Ig-like receptors on circulating natural killer cells

Head Neck. 2003 Apr;25(4):297-305. doi: 10.1002/hed.10198.


Background: In a group of patients with head and neck cancers (H&NC), the expansion of the population of CD3-,CD16+ natural killer (NK) cells in the peripheral blood was studied.

Methods: Cytofluorimetric analysis of the expression of killer Ig-like receptors (KIR, namely p58.1, p58.2, p58.3, p70, and p140) and CD94-NKG2a was performed. Cytolytic activities were studied using 51Cr release assay. T and NK cell cloning was performed using limiting dilution culture conditions. Cytokine production was analyzed using commercial enzyme immunoassays.

Results: Phenotypic analysis showed that the expanded populations were heterogeneous. Even in the presence of a large number of circulating NK cells, "nonspecific" cytolytic capacities were heavily reduced, whereas cytolytic capacity related to T cells was virtually normal. Unlike NK cell clones derived from healthy donors, most NK cells derived from H&NC patients expressed surface "activating" NK cell receptors (KAR) for HLA, detected by use of a redirected cytolytic assay. Analysis of the CD4+ subpopulation at the clonal level demonstrated that they had a severe proliferative defect.

Conclusion: These experimental data indicated that H&NC patients have a polyclonal expansion of functionally deficient NK cells expressing KAR. In addition, the proliferative capacity of patients' "helper" cells was strongly inhibited, thus accounting for a severe impairment of cytolytic activity of the expanded NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Head and Neck Neoplasms / blood*
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Killer Cells, Natural / immunology*
  • Lymphocyte Count
  • Male
  • Phenotype
  • Receptors, Immunologic / blood*
  • Receptors, Immunologic / genetics
  • Receptors, KIR
  • Receptors, KIR2DL3
  • Time Factors


  • KIR2DL3 protein, human
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL3
  • p70 natural killer cell receptor