| Literature DB >> 27478039 |
Jessica Endig1, Laura Elisa Buitrago-Molina1, Silke Marhenke1, Florian Reisinger2, Anna Saborowski1, Jutta Schütt3, Florian Limbourg4, Christian Könecke5, Alina Schreder5, Alina Michael1, Ana Clara Misslitz1, Marc Eammonn Healy6, Robert Geffers7, Thomas Clavel8, Dirk Haller8, Kristian Unger9, Milton Finegold10, Achim Weber6, Michael P Manns1, Thomas Longerich11, Mathias Heikenwälder12, Arndt Vogel13.
Abstract
Hepatocellular carcinoma (HCC) represents a classic example of inflammation-linked cancer. To characterize the role of the immune system in hepatic injury and tumor development, we comparatively studied the extent of liver disease and hepatocarcinogenesis in immunocompromised versus immunocompetent Fah-deficient mice. Strikingly, chronic liver injury and tumor development were markedly suppressed in alymphoid Fah(-/-) mice despite an overall increased mortality. Mechanistically, we show that CD8(+) T cells and lymphotoxin β are central mediators of HCC formation. Antibody-mediated depletion of CD8(+) T cells as well as pharmacological inhibition of the lymphotoxin-β receptor markedly delays tumor development in mice with chronic liver injury. Thus, our study unveils distinct functions of the immune system, which are required for liver regeneration, survival, and hepatocarcinogenesis.Entities:
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Year: 2016 PMID： 27478039 DOI： 10.1016/j.ccell.2016.06.009
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743