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

Kyo Chul Koo, Doo Hee Shim, Chang Mo Yang, Saet Byul Lee, Shi Mun Kim, Tae Young Shin, Kwang Hyun Kim, Ho Geun Yoon, Koon Ho Rha, Jae Myun Lee, Sung Joon Hong

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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 +CD56dim and CD16-CD56bright cells gated on CD56+CD3- cells were analyzed using a flow-cytometer. Results: NKA and the proportion of CD56bright 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 CD56dim-to-CD56bright 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 CD56bright cells in relation to the alteration of CD56dim 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 CD56bright 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.

Original languageEnglish
Article numbere78049
JournalPloS one
Volume8
Issue number11
DOIs
Publication statusPublished - 2013 Nov 4

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Koo, K. C., Shim, D. H., Yang, C. M., Lee, S. B., Kim, S. M., Shin, T. Y., Kim, K. H., Yoon, H. G., Rha, K. H., Lee, J. M., & Hong, S. J. (2013). Reduction of the CD16-CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer. PloS one, 8(11), [e78049]. https://doi.org/10.1371/journal.pone.0078049