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目的:探索胰岛素样生长因子结合蛋白质2(IGFBP2)对胰腺癌进展及其免疫微环境的影响。方法:胰腺癌及癌旁正常胰腺组织取自2009年1月至2015年12月天津医科大学总医院的50例胰腺癌手术患者，利用免疫组化和qRT-PCR法检测组织中IGFBP2的表达，并分析其表达水平与临床肿瘤分期及预后的关系。以体重20～25 g健康雄性C57BL/6小鼠建立IGFBP2过表达组和对照组原位胰腺癌小鼠模型各23只，建模后不同时间测量小鼠胰腺癌生长及肝转移情况，并通过流式细胞术检测肿瘤浸润性免疫细胞亚群变化。结果:免疫组化结果显示IGFBP2在人癌旁正常胰腺组织中表达阴性，在胰腺癌组织中表达阳性，其中高表达28例，低表达22例。qRT-PCR结果显示IGFBP2在人胰腺癌组织中的表达水平(11.01±5.07)较对应的癌旁正常胰腺组织(1.26±0.55)升高，差异具有统计学意义(n P<0.05)。IGFBP2低表达和高表达患者中TNM分期为T1-2期的比例分别为68.1%(15/22)和46.4%(13/28)，且IGFBP2低表达患者总生存期显著好于高表达患者(中位生存期20.5个月比8.0个月)，差异均具有统计学意义(n P<0.05)。IGFBP2过表达组荷瘤小鼠胰腺癌组织的最大截面积(181.10±18.86)mmn 2、肿瘤重量(0.64±0.15)g和肝脏转移灶数量(2.75±1.39)个均大于对照组(150.30±18.01)mmn 2、(0.41±0.11)g、(0.63±0.74)个，但生存期短于对照组(中位生存期38.0 d比36.0 d)，差异均具有统计学意义(均n P<0.05)。IGFBP2过表达组荷瘤小鼠胰腺癌组织较对照组胰腺癌组织中的M2/M1巨噬细胞比例、调节性T细胞比例上升，CD8n ＋ T细胞比例下降，CD8n ＋ T细胞中凋亡细胞比例上升，差异均具有统计学意义(均n P<0.05)。n 结论:IGFBP2通过诱导免疫抑制性肿瘤微环境促进胰腺癌进展。“,”Objective:To explore the effect of insulin-like growth factor-binding protein 2 (IGFBP2) on the progression of pancreatic ductal adenocarcinoma (PDAC) and the immune microenvironment.Methods:Tumor samples were obtained from 50 patients who underwent surgical resection at Tianjin Medical University General Hospital between January 2009 and December 2015 and diagnosed as PDAC. Immunohistochemistry and qRT-PCR were used to detect IGFBP2 expression in tumor tissues and adjacent normal tissues of PDAC patients. The correlations between IGFBP2 expression level and prognosis of PDAC patients were analyzed. Panc02-EV or Panc02-IGFBP2 cells were injected into the pancreas of C57BL/6 mice to establish orthotopic PDAC mouse models. The mice were sacrificed and the xenograft tumors were harvested and measured. The metastatic tumor in the liver were also analyzed. The tumors were dissociated into single-cell suspensions and processed for flow cytometry analysis to determine mouse M1 TAMs, M2 TAMs, T-regs, cytotoxic T cells, and apoptotic T cells.Results:According with the Immunohistochemistry data, it’s shown that IGFBP2 expression was negative in normal pancreatic tissues, but positive in pancreatic cancer tissues. There were 28 cases with IGFBP2 high and 22 cases with IGFBP2 low. qRT-PCR revealed that the expression of IGFBP2 in human pancreatic cancer tissues (11.01±5.07) was significantly higher (n P<0.05) than that in the corresponding adjacent normal tissues (1.26±0.55). The proportion of T1-2 stage in patients with IGFBP2 low and high was 68.1% (15/22) and 46.4% (13/28), respectively. The overall survival of patients with low IGFBP2 was better than that of patients with high IGFBP2 (median survival time was 20.5 months vs 8.0 months,n P<0.05). The maximum tumor area (181.10±18.86) mmn 2, tumor weight (0.64±0.15) g and number of liver metastases (2.75±1.39) in IGFBP2 overexpression group were significantly higher than those in control group (150.30±18.01) mmn 2, (0.41±0.11) g, (0.63±0.74), but the overall survival was worse than that of the control group (median survival time was 38.0 d vs 36.0 d, n P<0.05). Compared with the control group, the ratio of M2 macrophages and regulatory T cells in the IGFBP2 overexpression group increased, the proportion of CD8n + T cells decreased, and the proportion of apoptotic CD8n + T cells increased in IGFBP2 overexpression group (n P<0.05).n Conclusion:IGFBP2 promotes the progression of pancreatic ductal adenocarcinoma by reprograming immunosuppressive tumor microenvironment.