NK cell phenotypic modulation in lung cancer environment.

NK cell phenotypic modulation in lung cancer environment.
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肺癌环境中 NK 细胞表型调节。

DOI:
10.1371/journal.pone.0109976
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhou QH
Zhou QH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jin S;Deng Y;Hao JW;Li Y;Liu B;Yu Y;Shi FD;Zhou QH

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自然杀伤(NK)细胞在抗肿瘤免疫治疗中发挥着重要作用。但这表明肿瘤细胞可能通过肿瘤微环境中的某些分子机制影响NK细胞的正常功能。我们的研究通过免疫荧光、流式细胞术和实时PCR分析了NK细胞表面标志物(NK细胞受体)的变化,以及共培养的小鼠脾NK细胞和人高/低肺癌细胞系的杀伤功能。此外,我们在SCID小鼠肺癌模型上验证了上述结果。我们发现肿瘤周围NK细胞的浸润与肺癌患者的预后相关。而肺癌组织中NK细胞浸润的数量与肺癌患者的病理类型、原发癌的大小、吸烟史及预后密切相关。肿瘤微环境中NK细胞抑制受体的表达显着增加,相反,NK细胞激活受体的表达大幅下降。肺癌患者的生存时间与肺癌中NK细胞的浸润程度呈正相关。因此,NKG2D、Ly49I的下调和NKG2A的上调可能表明免疫耐受机制并促进肿瘤环境中的转移。我们的研究将为肿瘤免疫治疗的临床策略提供更多理论。
Nature killer (NK) cells play an important role in anti-tumor immunotherapy. But it indicated that tumor cells impacted possibly on NK cell normal functions through some molecules mechanisms in tumor microenvironment. Our study analyzed the change about NK cells surface markers (NK cells receptors) through immunofluorescence, flow cytometry and real-time PCR, the killed function from mouse spleen NK cell and human high/low lung cancer cell line by co-culture. Furthermore we certificated the above result on the lung cancer model of SCID mouse. We showed that the infiltration of NK cells in tumor periphery was related with lung cancer patients' prognosis. And the number of NK cell infiltrating in lung cancer tissue is closely related to the pathological types, size of the primary cancer, smoking history and prognosis of the patients with lung cancer. The expression of NK cells inhibitor receptors increased remarkably in tumor micro-environment, in opposite, the expression of NK cells activated receptors decrease magnificently. The survival time of lung cancer patient was positively related to NK cell infiltration degree in lung cancer. Thus, the down-regulation of NKG2D, Ly49I and the up-regulation of NKG2A may indicate immune tolerance mechanism and facilitate metastasis in tumor environment. Our research will offer more theory for clinical strategy about tumor immunotherapy.
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