Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer.
Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer.
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DOI：
10.1371/journal.pone.0078049
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hong SJ
中科院分区：
文献类型：
--
作者：
Koo KC;Shim DH;Yang CM;Lee SB;Kim SM;Shin TY;Kim KH;Yoon HG;Rha KH;Lee JM;Hong SJ
由自然杀伤（NK）细胞介导的天然细胞毒性在抑制和消除恶性肿瘤细胞中发挥着重要作用。为了研究 NK 细胞的免疫调节作用及其作为诊断标记物的潜力，对前列腺癌 (PCa) 患者的 NK 细胞活性 (NKA) 进行了分析，特别关注 NK 细胞亚群的分布。 NKA 和 NK 细胞亚群分布模式的前瞻性数据是从 51 名最初诊断为 PCa 的患者和 54 名健康对照中测量的。 NKA 用 Promoca® 刺激外周血后的 IFN-γ 水平来表示。为了确定 NK 细胞亚群的分布，用荧光染料偶联的单克隆抗体对 PBMC 进行染色。然后，使用流式细胞仪分析在 CD56+CD3− 细胞上门控的 CD16+CD56dim 和 CD16−CD56bright 细胞。与对照组相比，PCa 患者的 NKA 和 CD56bright 细胞比例显着降低（分别为 430.9 pg/ml vs. 975.2 pg/ml 和 2.3% vs. 3.8%；p<0.001）。两者均随着癌症分期的进展而逐渐下降（趋势p= 0.001）。在 PCa 患者中观察到 CD56dim 与 CD56bright 细胞的比率显着较高（41.8 vs. 30.3；p<0.001），并且随着癌症分期进展而逐渐增加（p 为趋势 = 0.001），这意味着与 CD56dim 细胞的改变相关的 CD56bright 细胞显着减少。 NKA 对 PCa 检测的敏感性和特异性分别为 72% 和 74%（最佳截止值为 530.9 pg/ml，AUC = 0.786）。 CD56bright 细胞的减少可能先于 NK 细胞功能障碍，导致针对 PCa 细胞的细胞毒性受损。这些观察结果可能解释了 PCa 微环境中观察到的 NK 细胞功能障碍背后的机制之一，并为未来癌症免疫治疗策略的发展提供支持。
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. 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. 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). 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.
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