Inflammation-induced IgA+ Cells Dismantle Anti-liver Cancer Immunity

Overview

Journal Nature

Specialty Science

Date 2017 Nov 17

PMID 29144460

Citations 282

Authors

Shabnam 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

Affiliations

Soon will be listed here.

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.

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