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Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer
Kyo Chul Koo1, Doo Hee Shim, Chang Mo Yang
1Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
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.
Insights
Natural killer (NK) cell activity and CD56(bright) cells are significantly reduced in prostate cancer (PCa) patients, correlating with disease progression. This suggests NK cell dysfunction may contribute to PCa development and offers potential for immunotherapeutic strategies.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Natural killer (NK) cells are crucial for eliminating malignant tumor cells.
- Investigating NK cell activity (NKA) and subset distribution in prostate cancer (PCa) can reveal immunoregulatory roles and diagnostic potential.
Purpose of the Study:
- To analyze NK cell activity (NKA) and NK cell subset distribution in prostate cancer (PCa) patients.
- To explore the potential of NKA and NK cell subsets as diagnostic markers for PCa.
Main Methods:
- Measured NKA via IFN-γ levels and analyzed NK cell subsets (CD16(+)CD56(dim), CD16(-)CD56(bright)) using flow cytometry in 51 PCa patients and 54 controls.
- Compared NKA and NK cell subset patterns between PCa patients and healthy individuals.
Main Results:
- PCa patients exhibited significantly lower NKA and a reduced proportion of CD56(bright) cells compared to controls (p<0.001).
- Both NKA and CD56(bright) cell levels decreased with advancing cancer stage (p for trend = 0.001).
- PCa patients showed a higher CD56(dim)-to-CD56(bright) cell ratio, indicating a relative decrease in CD56(bright) cells. NKA demonstrated 72% sensitivity and 74% specificity for PCa detection (AUC = 0.786).
Conclusions:
- Reduced CD56(bright) cells may precede NK cell dysfunction and impaired cytotoxicity in PCa.
- These findings elucidate mechanisms of NK cell dysfunction in the PCa microenvironment.
- The study supports the development of novel cancer immunotherapeutic strategies targeting NK cells.

