PUBLICATION HIGHLIGHT

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

Researchers from the UCSD Superfund Research Center in an impressive collaborative study, have found that chronic liver inflammation can also promote cancer by suppressing immunosurveillance — a natural defense mechanism in which it’s thought the immune system suppresses cancer development.

The study, led by Drs. Michael Karin (Distinguished Professor of Pharmacology and Pathology) and Shabnam Shalapour (Assistant Professor of Pharmacology), have shown 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.

Dr. Michael Karin indciated that “This study provides one of the strongest and most direct demonstrations that adaptive immunity actively prevents liver cancer.”

The researchers found that NASH-associated mutations provoke the immune system, including cytotoxic T cells, to recognize and attack the newly emerging cancer cells. However, chronic liver inflammation in both mice and humans also led to the accumulation of immunosuppressive lymphocytes, a type of immune cell Karin and Shalapour first described two years ago.

The study highlighted is published online November 8, 2017 in Nature

READ ENTIRE UC San Diego Health Press Release by UCSD Media Contact, Heather Buschman
Photo credit: NIH

Study co-authors also include: Ingmar N. Bastian, Alexander A. Aksenov, Alison F. Vrbanac, Weihua Li, Andres Perkins, Zhenyu Zhong, Debanjan Dhar, Jose A. Navas-Molina, Jun Xu, Rohit Loomba, Pieter C. Dorrestein, Rob Knight, Christopher Benner, UC San Diego; Xue-Jia Lin, UC San Diego and Jinan University; John Brain, Quentin M. Anstee, Newcastle University; Alastair D. Burt, University of Adelaide; Takaji Matsutani, Repertoire Genesis Incorporation; Michael Downes, Ruth T. Yu, Ronald M. Evans, Salk Institute for Biological Studies.

This research was funded, in part, by the National Institutes of Health (R01AI043477), Superfund Research Program (P42ES010337), European Union’s Horizon2020 Framework Program, Newcastle NIHR Biomedical Research Centre, UC San Diego Center for Microbiome Innovation, Irvington-CRI, PCF Young Investigator Award, SCRC, ALF Liver Scholar Award.

Published study:

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.  Inflammation-induced IgA cells dismantle anti-liver cancer immunity. Nature, 2017.  doi: 10.1038/nature24302    PMID: 29144460  |  PMCID: PMC5884449

For more information, please visit the following UCSD Superfund Research Projects and Cores:

Project 1, Dr. Michael Karin
Project 2, Dr. Ronald M. Evans
Project 4, Dr. Rohit Loomba
Genetics and Metabolomics Core, Dr. Christopher Benner