Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer.
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.
Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Kyo Chul
KC
Koo
Doo Hee
DH
Shim
Chang Mo
CM
Yang
Saet-Byul
SB
Lee
Shi Mun
SM
Kim
Tae Young
TY
Shin
Kwang Hyun
KH
Kim
Ho Geun
HG
Yoon
Koon Ho
KH
Rha
Jae Myun
JM
Lee
Sung Joon
SJ
Hong
D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism*; D016022:Case-Control Studies; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology*; D012372:ROC Curve; D017452:Receptors, IgG / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C522918:NCAM1 protein, human; D017452:Receptors, IgG