Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, 250012 Jinan, China.
Cancer Immunol Immunother. 2012 Jan;61(1):101-8. doi: 10.1007/s00262-011-1094-3. Epub 2011 Aug 19.
The overexpression of B7-H1 in hepatocellular carcinoma (HCC) mediates HCC immune escape and obstructs the immunotherapy based on tumor-specific CD8+ T cells. Tumor-associated macrophages (TAM) are a major component of cancer-related inflammation and play a central role in tumor promotion. To classify the mechanism underlying the overexpression of B7-H1 in HCC, we examined B7-H1 expression and TAM infiltration in 63 cases of human HCC samples using immunohistochemistry method and found that B7-H1 overexpression was associated with TAM infiltration in HCC tissues. Furthermore, B7-H1 expression was upregulated at both mRNA level and protein level in HCC cells (BEL-7402 and SMMC-7721) cocultured with macrophages in a transwell system. The upregulation of B7-H1 expression induced by macrophage was inhibited by blocking NF-κB or STAT3 signal pathways. These results suggest that overexpression of B7-H1 in HCC may be induced by inflammatory microenvironment involving macrophages and imply that anti-inflammation therapy might be preventive for immune escape and assistant for immunotherapy of HCC.
B7-H1 在肝细胞癌 (HCC) 中的过度表达介导 HCC 免疫逃逸，并阻碍基于肿瘤特异性 CD8+ T 细胞的免疫治疗。肿瘤相关巨噬细胞 (TAM) 是癌症相关炎症的主要组成部分，在肿瘤促进中发挥核心作用。为了对 HCC 中 B7-H1 过度表达的机制进行分类，我们使用免疫组织化学方法检查了 63 个人 HCC 样本中的 B7-H1 表达和 TAM 浸润情况，发现 B7-H1 过度表达与 HCC 组织中的 TAM 浸润有关。此外，在巨噬细胞共培养的 Transwell 系统中，B7-H1 在 HCC 细胞（BEL-7402 和 SMMC-7721）中的表达在 mRNA 水平和蛋白水平上均上调。由巨噬细胞诱导的 B7-H1 表达上调被阻断 NF-κB 或 STAT3 信号通路所抑制。这些结果表明，HCC 中 B7-H1 的过度表达可能是由涉及巨噬细胞的炎症微环境诱导的，并暗示抗炎治疗可能有助于预防免疫逃逸和辅助 HCC 的免疫治疗。
