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Senescence surveillance of pre-malignant hepatocytes limits liver cancer development

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  • Tae-Won Kang

    (Helmholtz Centre for Infection Research, Inhoffenstrasse 7)

  • Tetyana Yevsa

    (Helmholtz Centre for Infection Research, Inhoffenstrasse 7
    Hannover Medical School, Dept. of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg-Strasse 1)

  • 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
    Hannover Medical School, Dept. of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg-Strasse 1)

  • Daniel Dauch

    (Helmholtz Centre for Infection Research, Inhoffenstrasse 7)

  • Anja Hohmeyer

    (Helmholtz Centre for Infection Research, Inhoffenstrasse 7
    Hannover Medical School, Dept. of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg-Strasse 1)

  • 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
    Institute of Virology, Helmholtz Centre Munich, Technical University Munich)

  • 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
    Hannover Medical School, Dept. of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg-Strasse 1)

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.

Suggested Citation

  • 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 & Siegfr, 2011. "Senescence surveillance of pre-malignant hepatocytes limits liver cancer development," Nature, Nature, vol. 479(7374), pages 547-551, November.
    • Handle: RePEc:nat:nature:v:479:y:2011:i:7374:d:10.1038_nature10599
    DOI: 10.1038/nature10599
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    Cited by:

    1. Vanessa Rousseau & Elias Einig & Chao Jin & Julia Horn & Mathias Riebold & Tanja Poth & Mohamed-Ali Jarboui & Michael Flentje & Nikita Popov, 2023. "Trim33 masks a non-transcriptional function of E2f4 in replication fork progression," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Ross J. Hill & Nazareno Bona & Job Smink & Hannah K. Webb & Alastair Crisp & Juan I. Garaycoechea & Gerry P. Crossan, 2024. "p53 regulates diverse tissue-specific outcomes to endogenous DNA damage in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Imanol Duran & Joaquim Pombo & Bin Sun & Suchira Gallage & Hiromi Kudo & Domhnall McHugh & Laura Bousset & Jose Efren Barragan Avila & Roberta Forlano & Pinelopi Manousou & Mathias Heikenwalder & Domi, 2024. "Detection of senescence using machine learning algorithms based on nuclear features," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Ines Sturmlechner & Chance C. Sine & Karthik B. Jeganathan & Cheng Zhang & Raul O. Fierro Velasco & Darren J. Baker & Hu Li & Jan M. Deursen, 2022. "Senescent cells limit p53 activity via multiple mechanisms to remain viable," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Lingzhi Li & Ting Xiang & Jingjing Guo & Fan Guo & Yiting Wu & Han Feng & Jing Liu & Sibei Tao & Ping Fu & Liang Ma, 2024. "Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1β-dependent macrophage activation and tubular cell senescence," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    6. Xiangli Jiang & Ali Hyder Baig & Giuliana Palazzo & Rossella Pizzo & Toman Bortecen & Sven Groessl & Esther A. Zaal & Cinthia Claudia Amaya Ramirez & Alexander Kowar & Daniela Aviles-Huerta & Celia R., 2024. "P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Yukinari Haraoka & Yuki Akieda & Yuri Nagai & Chihiro Mogi & Tohru Ishitani, 2022. "Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Rana Salam & Alexa Saliou & Franck Bielle & Mathilde Bertrand & Christophe Antoniewski & Catherine Carpentier & Agusti Alentorn & Laurent Capelle & Marc Sanson & Emmanuelle Huillard & Léa Bellenger & , 2023. "Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    9. Christel F. A. Ramirez & Daniel Taranto & Masami Ando-Kuri & Marnix H. P. Groot & Efi Tsouri & Zhijie Huang & Daniel Groot & Roelof J. C. Kluin & Daan J. Kloosterman & Joanne Verheij & Jing Xu & Seren, 2024. "Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    10. Kai Markus Schneider & Antje Mohs & Wenfang Gui & Eric J. C. Galvez & Lena Susanna Candels & Lisa Hoenicke & Uthayakumar Muthukumarasamy & Christian H. Holland & Carsten Elfers & Konrad Kilic & Caroli, 2022. "Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    11. Benjamin Assouline & Rachel Kahn & Lutfi Hodali & Reba Condiotti & Yarden Engel & Ela Elyada & Tzlil Mordechai-Heyn & Jason R. Pitarresi & Dikla Atias & Eliana Steinberg & Tirza Bidany-Mizrahi & Esthe, 2024. "Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8+ T cell activation and limit responsiveness to immunotherapy in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Nanase Igarashi & Kenichi Miyata & Tze Mun Loo & Masatomo Chiba & Aki Hanyu & Mika Nishio & Hiroko Kawasaki & Hao Zheng & Shinya Toyokuni & Shunsuke Kon & Keiji Moriyama & Yasuyuki Fujita & Akiko Taka, 2022. "Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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