Posted on November 8, 2017 by MFeiock
Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity
Study explains success of some types of cancer immunotherapy, provides new targets for the development of additional immunotherapies
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.
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.
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
UCSD Superfund Research Center
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