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

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 gamma 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 gamma RIIlow/- activated B cells. Early activation of monocytes in cancer environments is critical for the generation of semimature dendritic cells and subsequent Fc gamma RIIlow/- activated B cells. More importantly, the activated Fc gamma RIIlow/- B cells from HCC tumours, but not the resting Fc gamma RIIhigh B cells, without external stimulation suppress autologous tumour-specific cytotoxic T-cell immunity via IL-10 signals. Collectively, generation of Fc gamma RIIlow/- activated B cells may represent a mechanism by which the immune activation is linked to immune tolerance in the tumour milieu.