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Endig, J.* ; Buitrago-Molina, L.E.* ; Marhenke, S.* ; Reisinger, F. ; Saborowski, A.* ; Schütt, J.* ; Limbourg, F.* ; Könecke, C.* ; Schreder, A.* ; Michael, A.* ; Misslitz, A.C.* ; Healy, M.E.* ; Geffers, R.* ; Clavel, T.* ; Haller, D.* ; Unger, K. ; Finegold, M.* ; Weber, A.* ; Manns, M.P.* ; Longerich, T.* ; Heikenwälder, M.* ; Vogel, A.*

Dual role of the adaptive immune system in liver injury and hepatocellular carcinoma development.

Cancer Cell 30, 308-323 (2016)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Green
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hereditary Tyrosinemia Type-1; Hepatic-dysfunction; Tumor-development; T-cells; Hepatocytes; Cancer; Regeneration; Mice; Fumarylacetoacetate; Pathogenesis
Sprache
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Zeitschrift Cancer Cell
Quellenangaben Band: 30, Heft: 8, Seiten: 308-323 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Translational Metabolic Oncology (IDC-TMO)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
Radiation Sciences
PSP-Element(e) G-551600-001
G-501000-001
DOI 10.1016/j.ccell.2016.06.009
WOS ID WOS:000381282200013
Scopus ID 84979780581
PubMed ID 27478039
Erfassungsdatum 2016-08-04
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