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Chemokine (C‐X‐C motif) receptor 3–positive B cells link interleukin‐17 inflammation to protumorigenic macrophage polarization in human hepatocellular carcinoma
Author(s) -
Liu RuiXian,
Wei Yuan,
Zeng QiuHui,
Chan KaWo,
Xiao Xiao,
Zhao XiaoYu,
Chen MinMin,
Ouyang FangZhu,
Chen DongPing,
Zheng Limin,
Lao XiangMing,
Kuang DongMing
Publication year - 2015
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28020
Subject(s) - cxcr3 , proinflammatory cytokine , chemokine , cxcl10 , biology , cancer research , microbiology and biotechnology , immunology , chemokine receptor , inflammation
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 . Conclusion : 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.(H epatology 2015;62:1779–1790)