Macrophages induce CD47 upregulation via IL-6 and correlate with poor survival in hepatocellular carcinoma patients
Macrophages induce CD47 upregulation via IL-6 and correlate with poor survival in hepatocellular carcinoma patients
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巨噬细胞通过 IL-6 诱导 CD47 上调，并与肝细胞癌患者的不良生存相关
DOI：
10.1080/2162402x.2019.1652540
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发表时间：
2019-08-16
期刊：
影响因子：
7.2
通讯作者：
Xu, Jing
中科院分区：
文献类型：
--
作者：
Chen, Jing;Zheng, Dan-Xue;Xu, Jing
摘要CD 47参与吞噬细胞介导的肿瘤清除，但其在肝细胞癌（HCC）中的表达、临床意义和调控机制仍知之甚少。在本研究中，我们发现肿瘤细胞上CD 47表达的上调与HCC患者的总生存率和无复发生存率相关。CD 47+肿瘤组织中巨噬细胞（Mφs）浸润减少。机制研究表明，来源于肿瘤浸润性Mφ的IL-6可通过激活STAT 3通路上调肝癌细胞表面CD 47的表达。CD 47的中和或IL-6-STAT 3轴的破坏降低了肿瘤细胞逃避吞噬作用的能力。此外，在化疗药物存在的情况下，CD 47阻断可以增强Mφ介导的吞噬作用，并且具有较低CD 47表达的HCC患者更可能从辅助经导管动脉化疗栓塞（TACE）治疗中贝内。这些结果表明，Mφ源性IL-6负责肝癌细胞表面CD 47的表达，这可能是一个潜在的预后指标和预测患者可能受益于辅助TACE治疗。
ABSTRACT CD47 is known to be involved in phagocyte-mediated tumor clearance; however, its expression, clinical significance, and regulatory mechanism in hepatocellular carcinoma (HCC) remain poorly understood. In the present study, we found that upregulation of CD47 expression on tumor cells was correlated with poor overall survival and recurrence-free survival in patients with HCC. Abundance of macrophages (Mφs) infiltration was found in CD47+ tumor tissues. Mechanistic studies revealed that IL-6 derived from tumor-infiltrating Mφs could upregulate CD47 expression on hepatoma cells through activation of the STAT3 pathway. Neutralization of CD47 or disruption of the IL-6–STAT3 axis reduced the ability of tumor cells to escape phagocytosis. Moreover, CD47 blockade could enhance Mφ-mediated phagocytosis in the presence of chemotherapeutic drugs, and HCC patients with lower CD47 expression were more likely to benefit from adjuvant transcatheter arterial chemoembolization (TACE) treatment. These findings revealed that Mφ-derived IL-6 was responsible for CD47 expression on hepatoma cells, which might be served as a potential prognostic marker and a predictor for patients who might benefit from adjuvant TACE treatment.