The coexpression and clinical significance of costimulatory molecules B7-H1, B7-H3, and B7-H4 in human pancreatic cancer.
The coexpression and clinical significance of costimulatory molecules B7-H1, B7-H3, and B7-H4 in human pancreatic cancer.
复制标题
共刺激分子B7-H1、B7-H3、B7-H4在人胰腺癌中的共表达及其临床意义
DOI：
10.2147/ott.s66809
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发表时间：
2014
影响因子：
4
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Chen Y;Sun J;Zhao H;Zhu D;Zhi Q;Song S;Zhang L;He S;Kuang Y;Zhang Z;Li D
目的研究抑制性共刺激分子B7-H1、B7-H3和B7-H4在人胰腺癌中的表达，探讨其在肿瘤微环境中的作用机制和临床意义。患者与方法本研究对63例胰腺癌组织和12例正常胰腺组织进行了检查。患者在2000年12月至2010年8月期间入组研究。B7家族分子的表达水平和组织中肿瘤浸润淋巴细胞的密度用免疫组织化学分析表征。结果50%以上的患者表达B7-H1和B7-H4，近100%的患者表达B7-H3。B7-H1表达与肿瘤大小相关，B7-H3表达与淋巴结转移和分化程度相关，B7-H4表达与肿瘤大小、淋巴结转移和浸润深度相关。B7-H4高表达也与胰腺癌的生存率低相关。我们确定了这三种B7家族分子在胰腺癌患者术后生存预后中的价值，B7家族分子共表达较少的胰腺癌患者的生存率显著较高。B7-H1表达与CD 3 + T细胞和CD 8 + T细胞浸润强度呈负相关，B7-H4表达与CD 3 + T细胞浸润强度呈负相关，而与CD 8 + T细胞浸润强度无相关性。结论B7-H1、B7-H3和B7-H4参与胰腺癌的发生发展，三者的联合表达可能是一个有价值的预后指标。负调节T细胞浸润可能是B7家族分子在胰腺癌中的主要作用机制。
Aim We investigated the expression of the inhibitory costimulatory molecules B7-H1, B7-H3, and B7-H4 in human pancreatic cancer to define their clinical significance and mechanism in a tumor microenvironment. Patients and methods Sixty-three pancreatic cancer tissues and 12 normal pancreatic tissues were examined in our research. Patients were enrolled in the study between December 2000 and August 2010. Expression levels of the B7 family of molecules and densities of tumor-infiltrating lymphocytes in the tissues were characterized with immunohistochemical assays. Results More than 50% of the patients expressed B7-H1 and B7-H4, and nearly 100% of the patients expressed B7-H3. B7-H1 expression was correlated with tumor size, B7-H3 expression was correlated with lymph-node metastasis and differentiation grade, and B7-H4 expression was correlated with tumor size, lymph-node metastasis, and invasion depth. High B7-H4 expression was also correlated with poor survival in pancreatic cancer. We determined the value of these three B7 family molecules in the postoperative survival prognosis for patients with pancreatic cancer, and pancreatic cancer patients with less coexpression of the B7 family of molecules had a significantly higher survival rate. B7-H1 expression was found to be negatively related to the intensity of both CD3+ T cells and CD8+ T cells, and B7-H4 expression was negatively related to CD3+ T-cell infiltration intensity, but not to CD8+ T cells. Conclusion B7-H1, B7-H3, and B7-H4 are involved in pancreatic cancer progression, and their coexpression could be a valuable prognostic indicator. Negative regulation of T-cell infiltration might be the main mechanism of action of the B7 family of molecules in pancreatic cancer.