title: Chemokine (C-X-C motif) receptor 3-positive B cells link interleukin-17 inflammation to protumorigenic macrophage polarization in human hepatocellular carcinoma.
abstract: B cells consistently represent abundant cellular components in tumors; however, direct evidence supporting a role for B cells in the immunopathogenesis of human cancers is lacking, as is specific knowledge of their trafficking mechanisms. Here, we demonstrate that chemokine (C-X-C motif) receptor 3-positive (CXCR3(+)) B cells constitute approximately 45% of B-cell infiltrate in human hepatocellular carcinoma (HCC) and that their levels are positively correlated with early recurrence of HCC. These cells selectively accumulate at the invading edge of HCC and undergo further somatic hypermutation and immunoglobulin G-secreting plasma cell differentiation. Proinflammatory interleukin-17(+) cells are important for the induction of epithelial cell-derived CXCR3 ligands CXCL9, CXCL10, and CXCL11, which subsequently promote the sequential recruitment and further maturation of CXCR3(+) B cells. More importantly, we provide evidence that CXCR3(+) B cells, but not their CXCR3(-) counterparts, may operate in immunoglobulin G-dependent pathways to induce M2b macrophage polarization in human HCC. Depletion of B cells significantly suppresses M2b polarization and the protumorigenic activity of tumor-associated macrophages and restores the production of antitumorigenic interleukin-12 by those cells in vivo.
  
  
  CONCLUSIONS
  Selective recruitment of CXCR3(+) B cells bridges proinflammatory interleukin-17 response and protumorigenic macrophage polarization in the tumor milieu, and blocking CXCR3(+) B-cell migration or function may help defeat HCC.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.|State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Rui-Xian
authors.initials: RX
authors.lastname: Liu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qiu-Hui
authors.initials: QH
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ka-Wo
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Chen
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Fang-Zhu
authors.initials: FZ
authors.lastname: Ouyang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Dong-Ping
authors.initials: DP
authors.lastname: Chen
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.|State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Lao
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.|State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Kuang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000502:physiology*; D008113:Liver Neoplasms / Q000276:immunology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054367:Receptors, CXCR3 / Q000502:physiology*
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D054367:Receptors, CXCR3