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

Simple item page
dc.contributor.authorShalapour, S.
dc.contributor.authorLin, X.-J.
dc.contributor.authorBastian, I.N.
dc.contributor.authorBrain, J.
dc.contributor.authorBurt, A.D.
dc.contributor.authorAksenov, A.A.
dc.contributor.authorVrbanac, A.F.
dc.contributor.authorLi, W.
dc.contributor.authorPerkins, A.
dc.contributor.authorMatsutani, T.
dc.contributor.authorZhong, Z.
dc.contributor.authorDhar, D.
dc.contributor.authorNavas-Molina, J.A.
dc.contributor.authorXu, J.
dc.contributor.authorLoomba, R.
dc.contributor.authorDownes, M.
dc.contributor.authorYu, R.T.
dc.contributor.authorEvans, R.M.
dc.contributor.authorDorrestein, P.C.
dc.contributor.authorKnight, R.
dc.contributor.authoret al.
dc.date.issued2017
dc.description.abstractThe 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.
dc.description.statementofresponsibilityShabnam Shalapour, Xue-Jia Lin, Ingmar N. Bastian, John Brain, Alastair D. Burt, Alexander A. Aksenov, Alison F. Vrbanac, Weihua Li, Andres Perkins, Takaji Matsutani, Zhenyu Zhong, Debanjan Dhar, Jose A. Navas-Molina, Jun Xu, Rohit Loomba, Michael Downes, Ruth T. Yu, Ronald M. Evans, Pieter C. Dorrestein, Rob Knight, Christopher Benner, Quentin M. Anstee, Michael Karin
dc.identifier.citationNature, 2017; 551(7680):340-345
dc.identifier.doi10.1038/nature24302
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.orcidBurt, A.D. [0000-0002-3011-7774]
dc.identifier.urihttp://hdl.handle.net/2440/129230
dc.language.isoen
dc.publisherSpringer Nature
dc.rights© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
dc.source.urihttps://doi.org/10.1038/nature24302
dc.subjectPlasma cells
dc.titleInflammation-induced IgA⁺ cells dismantle anti-liver cancer immunity
dc.title.alternativeInflammation-induced IgA(+) cells dismantle anti-liver cancer immunity
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications