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

  • Endig J Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
  • Buitrago-Molina LE Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
  • Marhenke S Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
  • Reisinger F Institute of Virology, Technische Universität München, Helmholtz Zentrum Muenchen, 85764 Munich, Germany.
  • Saborowski A Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
  • Schütt J Department of Cardiology, Philipps University Marburg, 35037 Marburg, Germany.
  • Limbourg F Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany.
  • Könecke C Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.
  • Schreder A Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.
  • Michael A Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
  • Misslitz AC Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
  • Healy ME Institute of Surgical Pathology, University Hospital Zurich, 8091 Zürich, Switzerland.
  • Geffers R Department of Cell Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • Clavel T ZIEL Institute for Food and Health, Technische Universität München, 85764 Munich, Germany.
  • Haller D ZIEL Institute for Food and Health, Technische Universität München, 85764 Munich, Germany.
  • Unger K Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, 85764 Munich, Germany.
  • Finegold M Department of Pathology, Texas Children's Hospital, Houston, TX 77030, USA.
  • Weber A Institute of Surgical Pathology, University Hospital Zurich, 8091 Zürich, Switzerland.
  • Manns MP Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
  • Longerich T Institute of Pathology, Aachen University Hospital, 52074 Aachen, Germany.
  • Heikenwälder M Department of Cardiology, Philipps University Marburg, 35037 Marburg, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg, 69121 Heidelberg, Germany.
  • Vogel A Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: vogel.arndt@mh-hannover.de.
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  • 2016-08-02
Published in:
  • Cancer cell. - 2016
Adaptive Immunity
Animals
CD8-Positive T-Lymphocytes
Carcinogenesis
Carcinoma, Hepatocellular
Humans
Hydrolases
Liver Diseases
Liver Neoplasms
Liver Regeneration
Lymphotoxin-beta
Mice
English 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.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/96969
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