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

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From: Nature(Vol. 551, Issue 7680)
Publisher: Nature Publishing Group
Document Type: Report
Length: 18,840 words
Lexile Measure: 1520L

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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[sup.+]) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8[sup.+] T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8[sup.+] T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA[sup.+] 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[sup.+] T-lymphocyte activation as a tumour-promoting mechanism.

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Gale Document Number: GALE|A514634941