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Dendritic cell-elicited B-cell activation fosters immune privilege via IL-10 signals in hepatocellular carcinoma.


ABSTRACT: B cells are prominent components of human solid tumours, but activation status and functions of these cells in human cancers remain elusive. Here we establish that over 50% B cells in hepatocellular carcinoma (HCC) exhibit an Fc?RIIlow/- activated phenotype, and high infiltration of these cells positively correlates with cancer progression. Environmental semimature dendritic cells, but not macrophages, can operate in a CD95L-dependent pathway to generate Fc?RIIlow/- activated B cells. Early activation of monocytes in cancer environments is critical for the generation of semimature dendritic cells and subsequent Fc?RIIlow/- activated B cells. More importantly, the activated Fc?RIIlow/- B cells from HCC tumours, but not the resting Fc?RIIhigh B cells, without external stimulation suppress autologous tumour-specific cytotoxic T-cell immunity via IL-10 signals. Collectively, generation of Fc?RIIlow/- activated B cells may represent a mechanism by which the immune activation is linked to immune tolerance in the tumour milieu.

SUBMITTER: Ouyang FZ 

PROVIDER: S-EPMC5118541 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Dendritic cell-elicited B-cell activation fosters immune privilege via IL-10 signals in hepatocellular carcinoma.

Ouyang Fang-Zhu FZ   Wu Rui-Qi RQ   Wei Yuan Y   Liu Rui-Xian RX   Yang Dong D   Xiao Xiao X   Zheng Limin L   Li Bo B   Lao Xiang-Ming XM   Kuang Dong-Ming DM  

Nature communications 20161117


B cells are prominent components of human solid tumours, but activation status and functions of these cells in human cancers remain elusive. Here we establish that over 50% B cells in hepatocellular carcinoma (HCC) exhibit an FcγRII<sup>low/-</sup> activated phenotype, and high infiltration of these cells positively correlates with cancer progression. Environmental semimature dendritic cells, but not macrophages, can operate in a CD95L-dependent pathway to generate FcγRII<sup>low/-</sup> activat  ...[more]

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