Inflammation-induced IgA(+) cells dismantle anti-liver cancer immunity

Article

关键词: NONALCOHOLIC STEATOHEPATITIS;    HEPATOCELLULAR-CARCINOMA;    TARGETED DELETION;    DEFICIENT MOUSE;    KAPPA-B;    GENE;    EXPRESSION;    MICE;    IMMUNOTHERAPY;    FIBROSIS;   

DOI  :  10.1038/nature24302

来源: SCIE

【 摘 要 】

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-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8(+) T-lymphocyte activation as a tumour-promoting mechanism.

【 授权许可】

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