| First Author | Shalapour S | Year | 2017 |
| Journal | Nature | Volume | 551 |
| Issue | 7680 | Pages | 340-345 |
| PubMed ID | 29144460 | Mgi Jnum | J:254160 |
| Mgi Id | MGI:6101220 | Doi | 10.1038/nature24302 |
| Citation | Shalapour S, et al. (2017) Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature 551(7680):340-345 |
| abstractText | 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. |
