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Reduction of the CD16(-)CD56(bright) NK Cell Subset Precedes NK Cell Dysfunction in Prostate Cancer

Authors
 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 
Citation
 PLoS One, Vol.8(11) : e78049, 2013 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2013
MeSH
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*
Keywords
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*
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.
Files in This Item:
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DOI
10.1371/journal.pone.0078049
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Koo, Kyo Chul(구교철) ORCID logo https://orcid.org/0000-0001-7303-6256
Kim, Kwang Hyun(김광현)
Rha, Koon Ho(나군호) ORCID logo https://orcid.org/0000-0001-8588-7584
Shin, Tae Young(신태영)
Shim, Doo Hee(심두희) ORCID logo https://orcid.org/0000-0002-6696-7199
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Lee, Saet Byul(이샛별)
Lee, Jae Myun(이재면) ORCID logo https://orcid.org/0000-0002-5273-3113
Hong, Sung Joon(홍성준) ORCID logo https://orcid.org/0000-0001-9869-065X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88382
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