Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer
Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer
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DOI：
10.3892/or.2011.1201
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发表时间：
2011-05-01
期刊：
影响因子：
4.2
通讯作者：
Yamaue, Hiroki
中科院分区：
文献类型：
--
作者：
Iida, Takeshi;Iwahashi, Makoto;Yamaue, Hiroki
最近，与Th 1或Th 2细胞不同的产生IL-17的T细胞亚群已被描述为炎症和自身免疫性疾病以及癌症发展的关键参与者。在这项研究中，我们研究了IL-17和辅助性T细胞17（Th 17）相关细胞因子在胃癌组织中的表达水平，并评估其表达与血管生成及其临床病理参数的关系。取82例胃癌患者的癌组织及癌旁正常组织。通过实时RT-PCR定量IL-17、IL-21和IL-23 mRNA表达水平。采用免疫组化和免疫荧光双标记法检测肿瘤组织中Th 17细胞浸润、微血管密度和中性粒细胞浸润。IL-17、IL-21和IL-23 mRNA在肿瘤组织中的表达较癌旁正常组织明显上调。肿瘤组织中IL-17 mRNA和IL-21 mRNA的表达水平呈显著正相关。表达高水平IL-17 mRNA的肿瘤中血管内皮细胞和浸润中性粒细胞的数量显著大于表达低水平IL-17 mRNA的肿瘤。在肿瘤组织中，大多数CD 4（+）细胞用抗IL-17抗体染色。IL-17 mRNA在胃癌组织中的表达水平与肿瘤的深度、淋巴管浸润和淋巴结转移有关，提示IL-17与胃癌的进展密切相关。IL-17和调控IL-17的IL-21可能成为胃癌治疗的潜在靶点。
Recently, a subset of IL-17 producing T cells distinct from Th1 or Th2 cells has been described as key players in inflammation and autoimmune diseases as well as cancer development. In this study, we investigated the expression level of IL-17 and T helper 17 (Th17)-related cytokines in gastric cancer tissues and assessed the association of their expression with angiogenesis and their clinicopathological parameters. Tumor and adjacent normal tissues were obtained from 82 patients with gastric cancer. IL-17, IL-21 and IL-23 mRNA expression levels were quantified by real-time RT-PCR. Th17 infiltration, microvessel density and neutrophil infiltration in tumor tissues were examined by immunohistochemistry and double immunofluorescence histochemistry. Expression of IL-17, IL-21 and IL-23 mRNA was found to be significantly up-regulated in tumor tissues compared with adjacent normal tissues. The expression level of IL-17 mRNA strongly and positively correlated with that of IL-21 mRNA in tumor tissue. The number of vascular endothelial cells and infiltrating neutrophils was significantly larger in tumors expressing a high level of IL-17 mRNA than in tumors expressing a low level of IL-17 mRNA. In tumor tissues most CD4(+) cells were stained with anti-IL-17 antibody. The expression level of IL-17 mRNA in gastric tumors was associated with the depth of the tumors, lymph-vascular invasion and lymph node involvement, suggesting that IL-17 obviously was related to tumor progression. IL-17 and IL-21, which regulates IL-17, would be potential therapeutic targets for the treatment of gastric cancer.