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非小细胞肺癌患者中M1/M2肿瘤相关巨噬细胞(TAM)及Th1/Th2细胞因子谱的特征分析

Characterization of M1/M2 Tumour-Associated Macrophages (TAMs) and Th1/Th2 Cytokine Profiles in Patients with NSCLC.

作者信息

Almatroodi S A, McDonald C F, Darby I A, Pouniotis D S

机构信息

Cancer & Tissue Repair Laboratory, School of Medical Sciences, RMIT University, P.O. Box 71, Bundoora, Victoria, Australia, 3083.

Applied Medical Sciences College, Qassim University, Buraidah, Saudi Arabia.

出版信息

Cancer Microenviron. 2016 Apr;9(1):1-11. doi: 10.1007/s12307-015-0174-x. Epub 2015 Aug 30.

Abstract

Lung cancer is one of the most commonly reported cancers, and is known to be associated with a poor prognosis. The function of tumour-associated macrophages (TAMs) in lung cancer patients is multifaceted and the literature shows conflicting roles. (I) To analyze the Th1 and Th2 cytokine levels that contribute to the differentiation of M1 and M2 macrophage populations in the serum of patients with NSCLC versus non-cancer controls; and (II) To characterize the M1 and M2 macrophage populations within TAMs in different subtypes of NSCLC compared to non-tumour tissue. The Th1 and Th2 cytokine levels were analyzed in serum using the Bio-Plex assay. In addition, TAMs subsets from non-tumour and tumour tissues were analyzed using immunohistochemistry (IHC). The level of IL-1β, IL-4, IL-6 and IL-8 was found to be increased in the serum of patients with large cell carcinoma but not in other NSCLC subtypes compared to non-cancer controls. In addition, the expression of CD68 and M2 marker CD163 was found to be increased (P ≤ 0.0001) in all NSCLC subtypes compared to non-tumour tissues. In contrast, the expression of iNOS (M1 marker) was decreased in the tumour tissue of patients with adenocarcinoma (P ≤ 0.01) and squamous carcinoma (P ≤ 0.05) but not in large cell carcinoma compared to non-tumour tissue. The results of this study indicate that NSCLC might have the ability to alter phenotype within the lung tumour areas in the local environment (TAMs) but not in the bloodstream in the systemic environment (serum) except for large cell carcinoma.

摘要

肺癌是报告最为常见的癌症之一,已知其预后较差。肿瘤相关巨噬细胞(TAM)在肺癌患者中的功能具有多面性,文献显示其作用存在矛盾之处。(I)分析非小细胞肺癌(NSCLC)患者与非癌症对照者血清中有助于M1和M2巨噬细胞群体分化的Th1和Th2细胞因子水平;(II)与非肿瘤组织相比,对不同亚型NSCLC中TAM内的M1和M2巨噬细胞群体进行特征描述。使用Bio-Plex检测法分析血清中的Th1和Th2细胞因子水平。此外,采用免疫组织化学(IHC)分析非肿瘤和肿瘤组织中的TAM亚群。与非癌症对照者相比,发现大细胞癌患者血清中IL-1β、IL-4、IL-6和IL-8水平升高,但其他NSCLC亚型中未升高。此外,与非肿瘤组织相比,所有NSCLC亚型中CD68和M2标志物CD163的表达均升高(P≤0.0001)。相反,与非肿瘤组织相比,腺癌(P≤0.01)和鳞状细胞癌(P≤0.05)患者肿瘤组织中诱导型一氧化氮合酶(iNOS,M1标志物)的表达降低,但大细胞癌中未降低。本研究结果表明,除大细胞癌外,NSCLC可能有能力在局部环境(TAM)中的肺肿瘤区域内改变表型,但在全身环境(血清)的血流中则不然。

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