Institute of Medical Biotechnology, Medical College of Suzhou University, 708 Renmin Road, Suzhou, 215007, Jiangsu, China.
Cancer Immunol Immunother. 2010 Aug;59(8):1163-71. doi: 10.1007/s00262-010-0841-1. Epub 2010 Mar 24.
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-alpha, 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.
B7-H3 是 B7 家族分子的一员，在适应性免疫反应中发挥重要作用，并且在各种实验系统中被证明可以促进或抑制 T 细胞反应。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，其在癌症中的确切作用尚不清楚。在本研究中，我们通过免疫组织化学方法研究了 102 例接受结直肠癌（CRC）治疗的患者的病理标本中 B7-H3 的表达。在 54.3%的 CRC 患者的癌症组织中发现了强烈的 B7-H3 表达，而在相邻的正常结直肠组织中则表达很少。肿瘤中 B7-H3 的高表达与肿瘤分级较高呈正相关。此外，与 B7-H3 在抑制肿瘤免疫监视中的作用一致，B7-H3 在癌细胞中的表达与肿瘤巢和肿瘤基质中浸润性 T 淋巴细胞的强度呈负相关。此外，我们发现 CRC 患者血清中可溶性 B7-H3 的水平高于健康供体。随后发现，肿瘤促进炎症分子 TNF-α 显著增加了结肠癌细胞系中可溶性 B7-H3 的释放。因此，我们的数据表明，可溶性和膜结合的 B7-H3 蛋白均参与了结肠癌的进展和逃避癌症免疫监视。
