Shalapour, S.Lin, X.-J.Bastian, I.N.Brain, J.Burt, A.D.Aksenov, A.A.Vrbanac, A.F.Li, W.Perkins, A.Matsutani, T.Zhong, Z.Dhar, D.Navas-Molina, J.A.Xu, J.Loomba, R.Downes, M.Yu, R.T.Evans, R.M.Dorrestein, P.C.Knight, R.et al.2020-12-032020-12-032017Nature, 2017; 551(7680):340-3450028-08361476-4687http://hdl.handle.net/2440/129230The 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.en© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.Plasma cellsJournal article003007777110.1038/nature243020004153655000342-s2.0-85034443159387746Burt, A.D. [0000-0002-3011-7774]