Open AccessDendritic cell-elicited B-cell activation fosters immune privilege via IL-10 signals in hepatocellular carcinoma
Author(s) -
Fang-Zhu Ouyang,
Rui-Qi Wu,
Wei Yuan,
Rui-Xian Liu,
Dong Yang,
Xiao Xiao,
Limin Zheng,
Bo Li,
Xiang-Ming Lao,
Dong-Ming Kuang
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms13453
Subject(s) - immune system , cytotoxic t cell , cancer research , immune privilege , dendritic cell , cancer cell , immunology , biology , cancer , in vitro , biochemistry , genetics
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 low/− 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 low/− activated B cells. Early activation of monocytes in cancer environments is critical for the generation of semimature dendritic cells and subsequent FcγRII low/− activated B cells. More importantly, the activated FcγRII low/− B cells from HCC tumours, but not the resting FcγRII high B cells, without external stimulation suppress autologous tumour-specific cytotoxic T-cell immunity via IL-10 signals. Collectively, generation of FcγRII low/− activated B cells may represent a mechanism by which the immune activation is linked to immune tolerance in the tumour milieu.