Tumor-infiltrating macrophages express interleukin-25 and predict a favorable prognosis in patients with gastric cancer after radical resection.
Tumor-infiltrating macrophages express interleukin-25 and predict a favorable prognosis in patients with gastric cancer after radical resection.
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肿瘤浸润巨噬细胞表达白细胞介素25并预测胃癌根治术后患者的良好预后
DOI：
10.18632/oncotarget.7095
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发表时间：
2016-03-08
期刊：
影响因子：
--
通讯作者：
Zheng L
中科院分区：
文献类型：
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作者：
Li J;Liao Y;Ding T;Wang B;Yu X;Chu Y;Xu J;Zheng L
白细胞介素-25（IL-25）是最近发现的促炎性IL-17细胞因子家族的成员;然而，其在人类肿瘤中的作用在很大程度上仍然未知。本研究旨在探讨IL-25在胃癌原位组织中的细胞来源及其临床意义。结果表明，巨噬细胞（Mφ）是原位GC中IL-25的主要表达细胞（IL-25+）。此外，IL-25+细胞在GC组织的肿瘤内（IT）区域中高度富集（p < 0.001）。胃癌细胞株SGC 7901体外培养上清可诱导Mφ产生IL-25，其IT区IL-25的密度与其他效应免疫细胞（CD 4 + T细胞、CD 8 + T细胞和CD 103 +T细胞）的密度呈正相关（p < 0.01）。这表明巨噬细胞可能产生IL-25以在GC组织中创建抗肿瘤微环境。IL-25+IT细胞水平与组织学分级呈正相关（p < 0.001），并被发现是胃癌患者根治性切除术后良好生存的独立预测因子（p = 0.024）。这些发现表明IL-25+IT细胞可能是这些患者的新治疗靶点。
Interleukin-25 (IL-25) is a recently identified member of the proinflammatory IL-17 cytokine family; however, its role in human tumors remains largely unknown. The aim of this study was to investigate the cellular source and clinical significance of IL-25 in gastric cancer (GC) in situ. The results demonstrated that macrophages (Mφs) were the primary IL-25-expressing cells (IL-25+) in GC in situ. Moreover, IL-25+ cells were highly enriched in the intra-tumoral (IT) region of GC tissues (p < 0.001). The production of IL-25 in Mφs exposed to culture supernatant from gastric cancer cell line SGC7901 in vitro was induced by transforming growth factor-β1, and their density in the IT region was positively associated with those of other effector immune cells, namely, CD4+ T cells, CD8+ T cells and CD103+T cells (p < 0.01). This suggested that macrophages might produce IL-25 to create an antitumor micromilieu in GC tissues. The level of IL-25+IT cells was positively associated with histological grade (p < 0.001) and found to be an independent predictor of favorable survival (p = 0.024) in patients with GC after radical resection. These findings suggest that IL-25+IT cells may be a novel therapeutic target in those patients.