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

2.50
Hdl Handle:
http://hdl.handle.net/10033/618446
Title:
Dual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development.
Authors:
Endig, Jessica; Buitrago-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 ( 0000-0003-4409-016X ) ; Clavel, Thomas; Haller, Dirk; Unger, Kristian; Finegold, Milton; Weber, Achim; Manns, Michael P; Longerich, Thomas; Heikenwälder, Mathias; Vogel, Arndt
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Dual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development. 2016, 30 (2):308-23 Cancer Cell
Journal:
Cancer cell
Issue Date:
8-Aug-2016
URI:
http://hdl.handle.net/10033/618446
DOI:
10.1016/j.ccell.2016.06.009
PubMed ID:
27478039
Type:
Article
Language:
en
ISSN:
1878-3686
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorEndig, Jessicaen
dc.contributor.authorBuitrago-Molina, Laura Elisaen
dc.contributor.authorMarhenke, Silkeen
dc.contributor.authorReisinger, Florianen
dc.contributor.authorSaborowski, Annaen
dc.contributor.authorSchütt, Juttaen
dc.contributor.authorLimbourg, Florianen
dc.contributor.authorKönecke, Christianen
dc.contributor.authorSchreder, Alinaen
dc.contributor.authorMichael, Alinaen
dc.contributor.authorMisslitz, Ana Claraen
dc.contributor.authorHealy, Marc Eammonnen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorClavel, Thomasen
dc.contributor.authorHaller, Dirken
dc.contributor.authorUnger, Kristianen
dc.contributor.authorFinegold, Miltonen
dc.contributor.authorWeber, Achimen
dc.contributor.authorManns, Michael Pen
dc.contributor.authorLongerich, Thomasen
dc.contributor.authorHeikenwälder, Mathiasen
dc.contributor.authorVogel, Arndten
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.en
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

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