Senescence surveillance of pre-malignant hepatocytes limits liver cancer development

Tae-Won Kang, Tetyana Yevsa, Norman Woller, Lisa Hoenicke, Torsten Wuestefeld, Daniel Dauch, Anja Hohmeyer, Marcus Gereke, Ramona Rudalska, Anna Potapova, Marcus Iken, Mihael Vucur, Siegfried Weiss, Mathias Heikenwalder, Sadaf Khan, Jesus Gil, Dunja Bruder, Michael Manns, Peter Schirmacher, Frank Tacke, Michael Ott, Tom Luedde, Thomas Longerich, Stefan Kubicka and Lars Zender ()
Additional contact information
Tae-Won Kang: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Tetyana Yevsa: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Norman Woller: Hannover Medical School, Dept. of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg-Strasse 1
Lisa Hoenicke: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Torsten Wuestefeld: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Daniel Dauch: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Anja Hohmeyer: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Marcus Gereke: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Ramona Rudalska: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Anna Potapova: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Marcus Iken: Twincore Centre for Experimental and Clinical Infection Research, Feodor-Lynen Strasse 7
Mihael Vucur: University Hospital Aachen
Siegfried Weiss: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Mathias Heikenwalder: University Hospital Zurich
Sadaf Khan: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus
Jesus Gil: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus
Dunja Bruder: Helmholtz Centre for Infection Research, Inhoffenstrasse 7
Michael Manns: Hannover Medical School, Dept. of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg-Strasse 1
Peter Schirmacher: University of Heidelberg, Institute of Pathology, Im Neuenheimer Feld 220/21
Frank Tacke: University Hospital Aachen
Michael Ott: Twincore Centre for Experimental and Clinical Infection Research, Feodor-Lynen Strasse 7
Tom Luedde: University Hospital Aachen
Thomas Longerich: University of Heidelberg, Institute of Pathology, Im Neuenheimer Feld 220/21
Stefan Kubicka: Clinic for Internal Medicine, District Hospital Reutlingen, Steinenbergstrasse 31
Lars Zender: Helmholtz Centre for Infection Research, Inhoffenstrasse 7

Nature, 2011, vol. 479, issue 7374, 547-551

Abstract: Senescence surveillance in cancer Oncogene-induced senescence has been shown to function as an intrinsic tumour suppressor mechanism. Lars Zender and colleagues now introduce the concept of 'senescence surveillance' by showing that premaligant senescent hepatocytes are cleared through a tumour antigen-directed immune response. This requires CD4+ T cells and suppresses the development of liver tumours in mouse models. The authors also provide evidence that senescent hepatocytes accumulate in the livers of immune-suppressed patients, demonstrating that senescence surveillance may also operate in humans. Strategies designed to harness antigen-specific immune surveillance of premalignant senescent cells may have potential in cancer prevention and therapy, and antigen-specific immune responses of this type may be relevant in vaccine production.

Date: 2011
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DOI: 10.1038/nature10599

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