Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma
Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2012.09.012
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发表时间：
2013-03-01
期刊：
影响因子：
4.8
通讯作者：
Batista, Aline Carvalho
中科院分区：
文献类型：
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作者：
Costa, Nadia Lago;Valadares, Marize Campos;Batista, Aline Carvalho
目的：探讨口腔鳞状细胞癌(OCSCC)肿瘤微环境中巨噬细胞群(M1/M2)的分布特征。分析巨噬细胞与口腔鳞癌患者生存期、淋巴结转移、肿瘤增殖、WHO组织学分级等临床病理因素的关系。材料和方法：手术切除的口腔鳞癌患者和正常口腔黏膜标本。采用免疫组织化学、流式细胞仪和定量逆转录聚合酶链式反应(qRT-PCR)检测巨噬细胞数量和细胞因子(IL-12、IL-23和INF-γ)和抗炎细胞因子(IL-10和TGF-β)的表达。结果：在口腔鳞癌的微环境中，M2表型(高比例的IL-10(+)、转化生长因子-β(+))巨噬细胞占优势。与健康人相比，口腔鳞癌组巨噬细胞表达转化生长因子-β的百分率较高。与对照组相比，口腔鳞状细胞癌组织中抗炎细胞因子转化生长因子β和白介素10的表达也明显增加。免疫组织化学显示转移组的巨噬细胞百分率显著高于未转移组和对照组。LOG-RANK检验还显示，高水平巨噬细胞患者的平均生存期(44个月)低于低巨噬细胞百分率患者(93个月)。结论：口腔鳞癌微环境中M2表型的优势可能通过产生转化生长因子-β而导致局部免疫抑制，从而增加淋巴转移，缩短患者的生存时间。(C)2012爱思唯尔有限公司。保留所有权利。
Objective: To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed.Materials and methods: The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-gamma) and anti-inflammatory (IL-10 and TGF-beta) cytokines. The level required for statistical significance was defined as p < 0.05.Results: The data showed a predominance of M2 phenotype (high percentage of IL-10(+)TGF-beta(+)) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-beta was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGF beta and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months).Conclusion: A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-beta production, and consequently greater lymph node involvement and reduced patient survival time. (C) 2012 Elsevier Ltd. All rights reserved.