Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity.

ABSTRACT: The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA⁺) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8⁺ T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8⁺ T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA⁺ cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-me

SUBMITTER: Shalapour S 

PROVIDER: S-EPMC5884449 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature