B Cells’ Role in Liver Cancer Explored

A recent study from the German Cancer Research Center (DKFZ) uncovered B cells’ role in driving the development of liver cancer in non-alcoholic steatohepatitis (NASH), an inflammatory fatty liver disease. Published in Nature Medicine, the study reveals that increased numbers of activated B cells were found in the gastrointestinal tract of both mice and humans with NASH.

The research team, led by Mathias Heikenwälder, found that B cells promote liver cancer development in NASH through two mechanisms. First, via direct cell-to-cell contact, B cells can activate autoaggressive T cells in the small intestine. This behavior was reproduced in vitro experiments, further emphasizing B cells’ influence on activating T cells. Additionally, B cells produce IgA class antibodies that activate specific immune cells, leading to liver fibrosis, a hallmark of NASH.

The team demonstrated that mice models genetically unable to produce B cells did not develop NASH when fed a high-fat diet, unlike mice able to produce B cells effectively. Furthermore, when the B cells were deactivated with an αCD20 antibody, inflammation and fibrosis regressed in the mice, resulting in fewer and smaller liver tumors.

To validate the findings in humans, the scientists analyzed tissue samples from NASH patients who had undergone weight-loss surgery. These samples exhibited increased levels of B cells and IgA, as well as increased activated macrophages in the gastrointestinal tissues.

“The good thing is that these results show us new ways to preventively interrupt this cancer-driving cascade,” explains Mathias Heikenwälder. “If we switch off the B cells with antibodies, the NASH symptoms regress and the animals develop fewer and smaller cancer foci. Fortunately, approved drugs already exist that suppress B-cell activation and that could possibly also stop NASH in humans and thus perhaps also liver cancer. However, there are no results from human studies on this yet.”