Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment.
Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment.
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DOI：
10.1186/s12885-015-1587-0
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发表时间：
2015-08-05
期刊：
影响因子：
3.8
通讯作者：
Ohmori Y
中科院分区：
文献类型：
--
作者：
Mori K;Haraguchi S;Hiori M;Shimada J;Ohmori Y
肿瘤相关巨噬细胞（TAM）参与各种实体瘤的生长、侵袭和转移。然而，实体瘤癌前病变中 TAM 的表型尚未明确。在本研究中，我们通过免疫组织化学分析鉴定了白斑（一种口腔癌前病变）中 TAM 的表型，并研究了参与 TAM 极化的浸润 T 细胞的参与情况。受试者包括 30 名口腔白斑患者和 10 名正常粘膜患者。检查苏木精和伊红玻片的组织学分级，并使用针对 CD68 (pan-MΦ)、CD80 (M1 MΦ)、CD163 (M2 MΦ)、CD4（辅助性 T 细胞：Th）、CD8（细胞毒性 T 细胞）、CXCR3、CCR5 (Th1)、CCR4 (Th2)、信号转导器和转录激活剂的抗体进行免疫组织化学分析(STAT1)、磷酸化 STAT1 (pSTAT1) 和趋化因子 CXCL9。使用Kruskal-Wallis检验测试不同组织学等级之间的阳性染色细胞数量的差异的统计显着性。使用斯皮尔曼等级分析确定不同类型免疫细胞之间的相关性。轻度和中度上皮不典型增生中CD163+ TAM浸润率增加，与上皮内CD4+ Th细胞浸润率呈正相关。尽管CCR4+细胞很少浸润，但在这些病变中观察到CXCR3+和CCR5+细胞。在相同的病变中还观察到 STAT1 和趋化因子 CXCL9、干扰素 (IFN) 诱导的基因产物和 pSTAT1 呈阳性的细胞。双重免疫荧光染色显示CD163阳性的细胞STAT1也呈阳性。口腔癌前病变中的 CD163+ TAM 共表达 CD163 和 STAT1，表明口腔癌前病变中的 TAM 在 Th1 主导的微环境中具有 M1 表型。
Tumor-associated macrophages (TAMs) are implicated in the growth, invasion and metastasis of various solid tumors. However, the phenotype of TAMs in premalignant lesions of solid tumors has not been clarified. In the present study, we identify the phenotype of TAMs in leukoplakia, an oral premalignant lesion, by immunohistochemical analysis and investigate the involvement of infiltrated T cells that participate in the polarization of TAMs. The subjects included 30 patients with oral leukoplakia and 10 individuals with normal mucosa. Hematoxylin and eosin slides were examined for the histological grades, and immunohistochemical analysis was carried out using antibodies against CD68 (pan-MΦ), CD80 (M1 MΦ), CD163 (M2 MΦ), CD4 (helper T cells: Th), CD8 (cytotoxic T cells), CXCR3, CCR5 (Th1), CCR4 (Th2), signal transducer and activator of transcription (STAT1), phosphorylated STAT1 (pSTAT1) and chemokine CXCL9. The differences in the numbers of positively stained cells among the different histological grades were tested for statistical significance using the Kruskal-Wallis test. Correlations between different types of immune cells were determined using Spearman’s rank analysis. An increase in the rate of CD163+ TAM infiltration was observed in mild and moderate epithelial dysplasia, which positively correlated with the rate of intraepithelial CD4+ Th cell infiltration. Although CCR4+ cells rarely infiltrated, CXCR3+ and CCR5+ cells were observed in these lesions. Cells positive for STAT1 and chemokine CXCL9, interferon- (IFN)-induced gene products, and pSTAT1 were also observed in the same lesions. Double immunofluorescence staining demonstrated that the cells that were positive for CD163 were also positive for STAT1. CD163+ TAMs in oral premalignant lesions coexpress CD163 and STAT1, suggesting that the TAMs in oral premalignant lesions possess an M1 phenotype in a Th1-dominated micromilieu.