Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer

PLoS One. 2013 Nov 4;8(11):e78049. doi: 10.1371/journal.pone.0078049. eCollection 2013.

Abstract

Background: Natural cytotoxicity, mediated by natural killer (NK) cells plays an important role in the inhibition and elimination of malignant tumor cells. To investigate the immunoregulatory role of NK cells and their potential as diagnostic markers, NK cell activity (NKA) was analyzed in prostate cancer (PCa) patients with particular focus on NK cell subset distribution.

Methods: Prospective data of NKA and NK cell subset distribution patterns were measured from 51 patients initially diagnosed with PCa and 54 healthy controls. NKA was represented by IFN-γ levels after stimulation of the peripheral blood with Promoca®. To determine the distribution of NK cell subsets, PBMCs were stained with fluorochrome-conjugated monoclonal antibodies. Then, CD16(+)CD56(dim) and CD16(-)CD56(bright) cells gated on CD56(+)CD3(-) cells were analyzed using a flow-cytometer.

Results: NKA and the proportion of CD56(bright) cells were significantly lower in PCa patients compared to controls (430.9 pg/ml vs. 975.2 pg/ml and 2.3% vs. 3.8%, respectively; p<0.001). Both tended to gradually decrease according to cancer stage progression (p for trend = 0.001). A significantly higher CD56(dim)-to-CD56(bright) cell ratio was observed in PCa patients (41.8 vs. 30.3; p<0.001) along with a gradual increase according to cancer stage progression (p for trend = 0.001), implying a significant reduction of CD56(bright) cells in relation to the alteration of CD56(dim) cells. The sensitivity and the specificity of NKA regarding PCa detection were 72% and 74%, respectively (best cut-off value at 530.9 pg/ml, AUC = 0.786).

Conclusions: Reduction of CD56(bright) cells may precede NK cell dysfunction, leading to impaired cytotoxicity against PCa cells. These observations may explain one of the mechanisms behind NK cell dysfunction observed in PCa microenvironment and lend support to the development of future cancer immunotherapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism*
  • CD56 Antigen / metabolism*
  • Case-Control Studies
  • GPI-Linked Proteins / metabolism
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Male
  • Middle Aged
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology*
  • ROC Curve
  • Receptors, IgG / metabolism*

Substances

  • Biomarkers, Tumor
  • CD56 Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • NCAM1 protein, human
  • Receptors, IgG

Grant support

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000807). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.