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Regulatory B cells accelerate hepatocellular carcinoma progression via CD40/CD154 signaling pathway

2014; Elsevier BV; Volume: 355; Issue: 2 Linguagem: Inglês

10.1016/j.canlet.2014.09.026

1872-7980

Yan Shao, Chung Mau Lo, Chang Chun Ling, Xiao Bing Liu, TP Ng, Andrew Chi Yuen Chu, Yuen Yuen, Chang Xian Li, Sheung Tat Fan, Kwan Man,

Cancer Immunotherapy and Biomarkers

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.