Preferential apoptosis of CD56dim natural killer cell subset in patients with cancer

Eur J Immunol. 2003 Jan;33(1):119-24. doi: 10.1002/immu.200390014.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Annexin A5 / metabolism
  • Apoptosis*
  • CD56 Antigen / metabolism*
  • Female
  • Humans
  • Killer Cells, Natural / metabolism*
  • Killer Cells, Natural / pathology*
  • Lymphocyte Subsets / metabolism
  • Lymphocyte Subsets / pathology
  • Male
  • Middle Aged
  • Neoplasms / immunology*
  • Neoplasms / pathology*
  • Protein Binding
  • Receptors, Interleukin-2 / metabolism
  • Tumor Cells, Cultured


  • Annexin A5
  • CD56 Antigen
  • Receptors, Interleukin-2