Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Cancer Lett. 2014 Dec 28;355(2):264-72. doi: 10.1016/j.canlet.2014.09.026. Epub 2014 Oct 6.
Human hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide with a poor prognosis of limited survival. The role of regulatory B cell (Breg), a new important B cell subset, in HCC progression remains unclear. We firstly found that the percentage of B cells at tumor margin was significantly higher than that in tumor and non-tumor regions. Especially, increased intrahepatic B cells at tumor margin were positively associated with tumor invasive features and more tumor recurrence. Besides, HCC patients had a significantly higher percentage of circulating Bregs than healthy people. Increased circulating Bregs were correlated with advanced tumor staging, tumor multiplicity and venous infiltration. Next, we firstly revealed that human Bregs promoted HCC tumor growth independent of Tregs in SCID mice. The migration of Bregs from blood into tumor was also confirmed in mice. Finally, we further explored the molecular mechanism of Bregs promoting proliferation and migration of HCC cells in vitro. Bregs promoted HCC growth and invasiveness by directly interacting with liver cancer cells through the CD40/CD154 signaling pathway.
人类肝细胞癌（HCC）是全球第五大常见癌症，预后较差，生存时间有限。调节性 B 细胞（Breg）作为一种新的重要 B 细胞亚群，其在 HCC 进展中的作用尚不清楚。我们首先发现，肿瘤边缘的 B 细胞比例明显高于肿瘤和非肿瘤区域。特别是，肿瘤边缘的肝内 B 细胞增加与肿瘤侵袭特征和更多的肿瘤复发呈正相关。此外，HCC 患者的循环 Breg 百分比明显高于健康人。循环 Bregs 的增加与肿瘤分期较晚、肿瘤多发性和静脉浸润相关。接下来，我们首次揭示了人类 Breg 在 SCID 小鼠中可独立于 Treg 促进 HCC 肿瘤生长。在小鼠中也证实了 Breg 从血液向肿瘤的迁移。最后，我们进一步探讨了 Breg 促进 HCC 细胞体外增殖和迁移的分子机制。Breg 通过 CD40/CD154 信号通路直接与肝癌细胞相互作用，促进 HCC 生长和侵袭。
