Clinical importance of B7-H3 expression in human pancreatic cancer.
Clinical importance of B7-H3 expression in human pancreatic cancer.
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DOI：
10.1038/sj.bjc.6605375
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发表时间：
2009-11-17
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
B7-H3是B7配体家族的新成员，在各种条件下调节T细胞应答。然而，B7-H3在肿瘤免疫中的作用在很大程度上是未知的。本研究的目的是评估B7-H3在人胰腺癌中表达的临床意义以及癌症免疫治疗的治疗潜力。我们通过免疫组化和实时荧光PCR检测了59例胰腺癌患者中B7-H3的表达。此外，我们在小鼠胰腺癌模型中检查了B7-H3阻断单克隆抗体的体内抗肿瘤作用。肿瘤相关B7-H3蛋白在胰腺癌组织中表达丰富，与非癌组织和正常胰腺组织相比表达明显增高。而且在有淋巴结转移和病理分期较晚的病例中表达更强。B7-H3阻断促进CD 8 + T细胞浸润到肿瘤中，并诱导对小鼠胰腺癌的显著抗肿瘤作用。此外，吉西他滨与B7-H3阻断剂的组合显示出协同抗肿瘤作用，而没有明显的毒性。我们的数据首次表明，B7-H3可能在胰腺癌中发挥关键作用，并为开发针对这种致命疾病的新型癌症免疫疗法提供了理论基础。
B7-H3 is a new member of the B7 ligand family and regulates T-cell responses in various conditions. However, the role of B7-H3 in tumour immunity is largely unknown. The purpose of this study was to evaluate the clinical significance of B7-H3 expression in human pancreatic cancer and the therapeutic potential for cancer immunotherapy. We investigated B7-H3 expression in 59 patients with pancreatic cancer by immunohistochemistry and real-time PCR. Furthermore, we examined the anti-tumour effect of B7-H3-blocking monoclonal antibody in vivo in a murine pancreatic cancer model. Tumour-related B7-H3 expression was abundant in most human pancreatic cancer tissues and was significantly higher compared with that in non-cancer tissue or normal pancreas. Moreover, its expression was significantly more intense in cases with lymph node metastasis and advanced pathological stage. B7-H3 blockade promoted CD8+ T-cell infiltration into the tumour and induced a substantial anti-tumour effect on murine pancreatic cancer. In addition, the combination of gemcitabine with B7-H3 blockade showed a synergistic anti-tumour effect without overt toxicity. Our data show for the first time that B7-H3 may have a critical role in pancreatic cancer and provide the rationale for developing a novel cancer immunotherapy against this fatal disease.
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