Dual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development.
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Authors
Endig, JessicaBuitrago-Molina, Laura Elisa
Marhenke, Silke
Reisinger, Florian
Saborowski, Anna
Schütt, Jutta
Limbourg, Florian
Könecke, Christian
Schreder, Alina
Michael, Alina
Misslitz, Ana Clara
Healy, Marc Eammonn
Geffers, Robert
Clavel, Thomas
Haller, Dirk
Unger, Kristian
Finegold, Milton
Weber, Achim
Manns, Michael P
Longerich, Thomas
Heikenwälder, Mathias
Vogel, Arndt
Issue Date
2016-08-08
Metadata
Show full item recordAbstract
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.Citation
Dual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development. 2016, 30 (2):308-23 Cancer CellAffiliation
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.Journal
Cancer cellPubMed ID
27478039Type
ArticleLanguage
enISSN
1878-3686ae974a485f413a2113503eed53cd6c53
10.1016/j.ccell.2016.06.009
Scopus Count
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/