@article{3daa463786fa45d98c6364094c3350b0,
title = "Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity",
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+) 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.",
author = "Shabnam Shalapour and Lin, {Xue Jia} and Bastian, {Ingmar N.} and John Brain and Burt, {Alastair D.} and Aksenov, {Alexander A.} and Vrbanac, {Alison F.} and Weihua Li and Andres Perkins and Takaji Matsutani and Zhenyu Zhong and Debanjan Dhar and Navas-Molina, {Jose A.} and Jun Xu and Rohit Loomba and Michael Downes and Yu, {Ruth T.} and Evans, {Ronald M.} and Dorrestein, {Pieter C.} and Rob Knight and Christopher Benner and Anstee, {Quentin M.} and Michael Karin",
note = "Funding Information: Acknowledgements We thank S. Choi, B. H. Dang, K. Nguyen, I. Mellman, G. Ackermann, H. Reeves, R. Quinn, G. Di Caro, G. Karin, and J. Haybaeck for help and advice. The research was supported by the National Institutes of Health (NIH), National Institute of Environmental Health Sciences Superfund Research Program, Horizon-2020-Framework Program of the European Union (Q.M.A.), Newcastle NIHR Biomedical Research Centre, CMI seed grant, Irvington Cancer Research Institute (S.S., Z.Z.), Prostate Cancer Foundation Young Investigator Award (S.S.), Southern California Research Center for ALPD and Cirrhosis grant (S.S., I.N.B.), Prevent Cancer Foundation Board of Directors Research Award (Z.Z.), and American Liver Foundation liver scholar award (D.D.). M.K. holds the Ben and Wanda Hildyard Chair. NIH funding was as follows: CA127923, CA118165, AI043477, and U01AA022614 to M.K.; P41GM103484-07 and GMS10RR029121 to P.C.D.; P42ES010337 to M.K., R.M.E., and R.L.; DK106419 to R.L.; and EPoS-634413 to Q.M.A. Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2017",
month = nov,
day = "16",
doi = "10.1038/nature24302",
language = "English (US)",
volume = "551",
pages = "340--345",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7680",
}