Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, 180 Feng Lin Road, Shanghai, 200032, People's Republic of China.
Cancer Immunol Immunother. 2012 Nov;61(11):2171-82. doi: 10.1007/s00262-012-1278-5. Epub 2012 May 22.
B7-H3, a novel B7 family member, positively or negatively regulates T-cell responses. We investigated the clinical relevance and prognostic significance of B7-H3 in hepatocellular carcinoma (HCC). Western blotting showed B7-H3 upregulation in 17 of 24 (70.8 %) HCC tissues compared with nontumor liver tissues (p = 0.028). B7-H3 immunostaining on tissue microarrays containing 240 HCC patient samples indicated that 225 (93.8 %) tumors had aberrant B7-H3 expression, with strong intensity in 79 (32.9 %) cases, whereas B7-H3 expression in peritumor liver cells was weak in most cases (226; 94.2 %). Notably, patients with high/moderate tumor cell B7-H3 expression showed significantly poorer survival (p = 0.009) and increased recurrence (p = 0.002). After multivariable adjustment, high/moderate B7-H3 expression remained significant for an increased risk of recurrence (hazard ratio = 1.79; 95 % confidence interval = 1.19-2.70; p = 0.005). B7-H3 expression correlated with invasive phenotypes like vascular invasion and advanced tumor stage, and the metastatic potential of HCC cell lines. Flow cytometry showed that B7-H3 expression is inversely correlated with proliferation and interferon-γ production by infiltrating T cells. Interferon-γ stimulation significantly upregulated B7-H3 expression in HCC cells in vitro, implicating B7-H3 expression as a feedback mechanism to evade anti-tumor immunity. Importantly, the prognostic value of B7-H3 expression was validated in an independent cohort of 206 HCC patients. Collectively, our data suggest that B7-H3 was abundantly expressed in HCC and was associated with adverse clinicopathologic features and poor outcome. Thus, B7-H3 represents an attractive target for diagnostic and therapeutic manipulation in human HCC.
B7-H3 是一种新型的 B7 家族成员，可正向或负向调节 T 细胞反应。我们研究了 B7-H3 在肝细胞癌（HCC）中的临床相关性和预后意义。Western blot 显示，与非肿瘤肝组织相比，24 例 HCC 组织中有 17 例（70.8%）B7-H3 上调（p=0.028）。包含 240 例 HCC 患者样本的组织微阵列的 B7-H3 免疫染色表明，225 例（93.8%）肿瘤存在异常的 B7-H3 表达，79 例（32.9%）肿瘤的表达强度较强，而大多数情况下肿瘤周围肝实质细胞的 B7-H3 表达较弱（226 例；94.2%）。值得注意的是，B7-H3 高/中度肿瘤细胞表达的患者生存明显较差（p=0.009），复发率增加（p=0.002）。多变量调整后，B7-H3 高/中度表达仍然是复发风险增加的显著因素（风险比=1.79；95%置信区间=1.19-2.70；p=0.005）。B7-H3 表达与血管侵犯和肿瘤晚期等侵袭表型以及 HCC 细胞系的转移潜能相关。流式细胞术显示，B7-H3 表达与浸润性 T 细胞的增殖和干扰素-γ产生呈负相关。体外干扰素-γ刺激显著上调 HCC 细胞中 B7-H3 的表达，表明 B7-H3 表达是逃避抗肿瘤免疫的反馈机制。重要的是，在另一组 206 例 HCC 患者中验证了 B7-H3 表达的预后价值。综上所述，我们的数据表明 B7-H3 在 HCC 中大量表达，并与不良的临床病理特征和不良预后相关。因此，B7-H3 是人类 HCC 诊断和治疗干预的一个有吸引力的靶点。
