Interleukin-17-Producing Neutrophils Link Inflammatory Stimuli to Disease Progression by Promoting Angiogenesis in Gastric Cancer
Interleukin-17-Producing Neutrophils Link Inflammatory Stimuli to Disease Progression by Promoting Angiogenesis in Gastric Cancer
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产生白细胞介素 17 的中性粒细胞通过促进胃癌血管生成将炎症刺激与疾病进展联系起来
DOI：
10.1158/1078-0432.ccr-16-0617
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发表时间：
2017-03-15
影响因子：
11.5
通讯作者：
Li, Guo-Xin
中科院分区：
文献类型：
--
作者：
Li, Tuan-Jie;Jiang, Yu-Ming;Li, Guo-Xin
目的：中性粒细胞水平升高与各种癌症的生存率差有关，但支持中性粒细胞在人类cancer.Experimental Design免疫发病机制中的作用的直接证据不足：共有573例胃癌患者参加了这项研究。采用免疫组化和实时荧光定量PCR分析不同显微解剖区域中性粒细胞的分布和临床意义。结果：胃癌患者外周血中性粒细胞计数升高与预后不良有关。在胃癌组织中，中性粒细胞主要富集在浸润边缘，中性粒细胞水平是胃癌患者生存率低的有力预测因子。IL 17（+）中性粒细胞构成人胃癌中IL 17产生细胞的大部分。促炎性IL 17是CXC趋化因子将中性粒细胞募集到浸润边缘的关键介质。此外，浸润边缘的中性粒细胞是基质金属蛋白酶-9的主要来源，基质金属蛋白酶-9是一种分泌的蛋白质，刺激胃癌细胞的促血管生成活性。因此，高水平的浸润性中性粒细胞在浸润边缘与血管生成进展的患者与gastric cancer.Conclusions：这些数据提供了直接的证据，支持中性粒细胞在胃癌进展的关键作用，揭示了一种新的免疫逃逸机制，涉及微调癌细胞和免疫细胞之间的协同作用，在不同的肿瘤微环境。(C)2016年AACR。
Purpose: Elevated levels of neutrophils have been associated with poor survival in various cancers, but direct evidence supporting a role for neutrophils in the immunopathogenesis of human cancers is lacking.Experimental Design: A total of 573 patients with gastric cancer were enrolled in this study. Immunohistochemistry and real-time PCR were performed to analyze the distribution and clinical relevance of neutrophils in different microanatomic regions. The regulation and function of neutrophils were assessed both in vitro and in vivo.Results: Increased neutrophil counts in the peripheral blood were associated with poor prognosis in gastric cancer patients. In gastric cancer tissues, neutrophils were enriched predominantly in the invasive margin, and neutrophil levels were a powerful predictor of poor survival in patients with gastric cancer. IL17(+) neutrophils constitute a large portion of IL17-producing cells in human gastric cancer. Proinflammatory IL17 is a critical mediator of the recruitment of neutrophils into the invasive margin by CXC chemokines. Moreover, neutrophils at the invasive margin were a major source of matrix metalloproteinase-9, a secreted protein that stimulates proangiogenic activity in gastric cancer cells. Accordingly, high levels of infiltrated neutrophils at the invasive margin were positively correlated with angiogenesis progression in patients with gastric cancer.Conclusions: These data provide direct evidence supporting the pivotal role of neutrophils in gastric cancer progression and reveal a novel immune escape mechanism involving fine-tuned collaborative action between cancer cells and immune cells in the distinct tumor microenvironment. (C) 2016 AACR.