title: Regulatory B cells accelerate hepatocellular carcinoma progression via CD40/CD154 signaling pathway.
abstract: 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.
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Chung Mau
authors.initials: CM
authors.lastname: Lo
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Chang Chun
authors.initials: CC
authors.lastname: Ling
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Xiao Bing
authors.initials: XB
authors.lastname: Liu
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Kevin Tak-Pan
authors.initials: KT
authors.lastname: Ng
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Andrew Chi Yuen
authors.initials: AC
authors.lastname: Chu
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Yuen Yuen
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Chang Xian
authors.initials: CX
authors.lastname: Li
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
authors.affiliation: Department of Surgery and Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Electronic address: kwanman@hku.hk.
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand
keywords: Bregs; HCC; Invasion