Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma
Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma
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共刺激分子B7-H3在人结直肠癌中的临床意义及调控
DOI：
10.1007/s00262-010-0841-1
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发表时间：
2010-08-01
影响因子：
5.8
通讯作者：
Zhang, Xue-guang
中科院分区：
文献类型：
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作者：
Sun, Jing;Chen, Lu-jun;Zhang, Xue-guang
B7-H3是B7家族分子的一员，在适应性免疫应答中起着重要作用，并且在各种实验系统中显示出促进或抑制T细胞应答。B7-H3在一些人类癌症中表达，并与癌症患者的不良预后相关。然而，它在癌症中的确切作用尚不清楚。本研究应用免疫组化方法检测了102例结直肠癌（CRC）组织中B7-H3的表达。B7-H3在54.3%的结直肠癌患者的癌组织中有较强的表达，而在癌旁正常结直肠组织中表达最低。B7-H3在肿瘤中的高表达与更晚期的肿瘤分级正相关。此外，与B7-H3在抑制肿瘤免疫监视中的作用一致，癌细胞中B7-H3的表达与肿瘤巢和肿瘤基质中肿瘤浸润T淋巴细胞的强度负相关。此外，我们还发现CRC患者血清中可溶性B7-H3的水平高于健康供体。TNF-α是一种重要的促癌炎症分子，随后发现可显著增加结肠癌细胞系中可溶性B7-H3的释放。因此，我们的数据表明，可溶性和膜B7-H3蛋白参与结肠癌的进展和逃避癌症免疫监视。
B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses, and was shown to either promote or inhibit T-cell responses in various experimental systems. B7-H3 was expressed in some human cancers and correlated with poor outcome of cancer patients. However, its exact role in cancer is not known. In the present study, we studied the expression of B7-H3 in the pathologic specimens of 102 patients treated for colorectal carcinoma (CRC) by immunohistochemistry. Strong B7-H3 expression was found in cancer tissues from 54.3% CRC patients, while minimal expression was found in adjacent normal colorectal tissues. Higher B7-H3 expression in tumor positively correlated with a more advanced tumor grade. In addition, consistent with a role of B7-H3 in suppressing tumor immune surveillance, the expression of B7-H3 in cancer cells negatively correlated with the intensity of tumor infiltrating T lymphocytes in both tumor nest and tumor stroma. Furthermore, we found that the level of soluble B7-H3 in sera from CRC patients was higher than healthy donors. TNF-α, an important cancer-promoting inflammatory molecule, was subsequently found to significantly increase the release of soluble B7-H3 in colon cancer cell lines. Therefore, our data suggest that both soluble and membranous B7-H3 proteins are involved in colon cancer progression and evasion of cancer immune surveillance.