Cancer

Patient sample and mouse studies suggest depleting IgA-positive plasma cells in the liver could help treat non-alcoholic steatohepatitis (NASH)-induced hepatocellular carcinoma (HCC). In liver samples from 18 NASH patients, IgA levels were associated with fibrosis, a risk marker for progression to HCC. In a mouse model of high-fat diet-induced NASH that progresses to HCC, knockout of IgA decreased tumor burden and increased CD8⁺ T cell activation in the liver compared with normal IgA expression. Also in the model, an anti-PD-L1 mAb decreased IgA-positive plasma cell numbers and tumor burden in the liver and increased CD8⁺ T cell activation in the liver compared with a control protein that bound but did not inhibit PD-L1, whereas in IgA-knockout models, the mAb had no effect on tumor growth. Next steps could include identifying the factors that recruit IgA-positive cells to the liver as potential therapeutic targets in NASH-induced HCC...