Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity
Menée à l'aide de modèles murins de stéatose hépatique, cette étude met en évidence des mécanismes de nature inflammatoire par lesquels, en supprimant des lymphocytes T CD8+ cytotoxiques, l'accumulation de cellules produisant l'immunoglobuline A dans le foie favorise le développement d'un carcinome hépatocellulaire
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.
Nature 2017