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

dc.contributor.authorEndig, Jessica
dc.contributor.authorBuitrago-Molina, Laura Elisa
dc.contributor.authorMarhenke, Silke
dc.contributor.authorReisinger, Florian
dc.contributor.authorSaborowski, Anna
dc.contributor.authorSchütt, Jutta
dc.contributor.authorLimbourg, Florian
dc.contributor.authorKönecke, Christian
dc.contributor.authorSchreder, Alina
dc.contributor.authorMichael, Alina
dc.contributor.authorMisslitz, Ana Clara
dc.contributor.authorHealy, Marc Eammonn
dc.contributor.authorGeffers, Robert
dc.contributor.authorClavel, Thomas
dc.contributor.authorHaller, Dirk
dc.contributor.authorUnger, Kristian
dc.contributor.authorFinegold, Milton
dc.contributor.authorWeber, Achim
dc.contributor.authorManns, Michael P
dc.contributor.authorLongerich, Thomas
dc.contributor.authorHeikenwälder, Mathias
dc.contributor.authorVogel, Arndt
dc.date.accessioned2016-08-16T14:40:20Z
dc.date.available2016-08-16T14:40:20Z
dc.date.issued2016-08-08
dc.identifier.citationDual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development. 2016, 30 (2):308-23 Cancer Cellen
dc.identifier.issn1878-3686
dc.identifier.pmid27478039
dc.identifier.doi10.1016/j.ccell.2016.06.009
dc.identifier.urihttp://hdl.handle.net/10033/618446
dc.description.abstractHepatocellular 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.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleDual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalCancer cellen
refterms.dateFOA2018-06-12T17:30:42Z
html.description.abstractHepatocellular 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.


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