| Literature DB >> 29144460 |
Shabnam Shalapour1, Xue-Jia Lin1,2, Ingmar N Bastian1, John Brain3, Alastair D Burt4, Alexander A Aksenov5, Alison F Vrbanac6, Weihua Li1, Andres Perkins1, Takaji Matsutani7, Zhenyu Zhong1, Debanjan Dhar1, Jose A Navas-Molina6, Jun Xu8, Rohit Loomba9, Michael Downes10, Ruth T Yu10, Ronald M Evans10, Pieter C Dorrestein5,11, Rob Knight6,11, Christopher Benner8, Quentin M Anstee3, Michael Karin1,11.
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.Entities:
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Year: 2017 PMID： 29144460 PMCID： PMC5884449 DOI： 10.1038/nature24302
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962