Dual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development

Publication date: Available online 28 July 2016
Source:Cancer Cell
Author(s): Jessica Endig, Laura Elisa Buitrago-Molina, Silke Marhenke, Florian Reisinger, Anna Saborowski, Jutta Schütt, Florian Limbourg, Christian Könecke, Alina Schreder, Alina Michael, Ana Clara Misslitz, Marc Eammonn Healy, Robert Geffers, Thomas Clavel, Dirk Haller, Kristian Unger, Milton Finegold, Achim Weber, Michael P. Manns, Thomas Longerich, Mathias Heikenwälder, Arndt Vogel
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.

Teaser

Endig et al. show that T lymphocytes play dual roles in hepatic injury and tumor development, both being suppressed in alymphoid Fah^−/− mice despite increase in overall mortality. Depletion of CD8⁺ T cells or inhibiting the lymphotoxin-β receptor delays tumors development in mice with chronic liver damage.


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