Steatohepatitis progresses to cancer via immunosuppression of HCC directed CD8+ T cells. Mus musculus

We show that chronic inflammation and fibrosis in mice with non-alcoholic fatty liver disease (NASH) is accompanied by accumulation of immunoglobulin A (IgA) positive plasmocytes. These cells suppress activation of cytotoxic T cells (CTL) derived from liver infiltrating CD8+ cells. CD8+ T cell ablation greatly accelerates HCC appearance, genetic or pharmacological targeting of IgA and PD-L1 expressing plasmocytes attenuates hepatic carcinogenesis and induces CTL-dependent regression of established HCC. Overall design: RNA were isolated from liver /tumor of healthy HFD-fed control mice, mice with NASH, and HCC, and were analyzed using RNA-seq.