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Loss of HIF-1α in natural killer cells inhibits tumour growth by stimulating non-productive angiogenesis

Author

Listed:
  • Ewelina Krzywinska

    (Paris Cardiovascular Research Center)

  • Chahrazade Kantari-Mimoun

    (Paris Cardiovascular Research Center)

  • Yann Kerdiles

    (Aix Marseille Université UM2)

  • Michal Sobecki

    (CEA/CNRS/Université Paris Sud)

  • Takayuki Isagawa

    (Nagasaki University)

  • Dagmar Gotthardt

    (University of Veterinary Medicine Vienna)

  • Magali Castells

    (Paris Cardiovascular Research Center)

  • Johannes Haubold

    (Universitätsklinikum Essen, Universität Duisburg-Essen)

  • Corinne Millien

    (Paris Cardiovascular Research Center)

  • Thomas Viel

    (Paris Cardiovascular Research Center)

  • Bertrand Tavitian

    (Paris Cardiovascular Research Center)

  • Norihiko Takeda

    (The University of Tokyo)

  • Joachim Fandrey

    (Universitätsklinikum Essen, Universität Duisburg-Essen)

  • Eric Vivier

    (Aix Marseille Université UM2
    Aix-Marseille Université)

  • Veronika Sexl

    (CEA/CNRS/Université Paris Sud)

  • Christian Stockmann

    (Paris Cardiovascular Research Center
    Institute of Anatomy, University of Zurich)

Abstract

Productive angiogenesis, a prerequisite for tumour growth, depends on the balanced release of angiogenic and angiostatic factors by different cell types within hypoxic tumours. Natural killer (NK) cells kill cancer cells and infiltrate hypoxic tumour areas. Cellular adaptation to low oxygen is mediated by Hypoxia-inducible factors (HIFs). We found that deletion of HIF-1α in NK cells inhibited tumour growth despite impaired tumour cell killing. Tumours developing in these conditions were characterised by a high-density network of immature vessels, severe haemorrhage, increased hypoxia, and facilitated metastasis due to non-productive angiogenesis. Loss of HIF-1α in NK cells increased the bioavailability of the major angiogenic cytokine vascular endothelial growth factor (VEGF) by decreasing the infiltration of NK cells that express angiostatic soluble VEGFR-1. In summary, this identifies the hypoxic response in NK cells as an inhibitor of VEGF-driven angiogenesis, yet, this promotes tumour growth by allowing the formation of functionally improved vessels.

Suggested Citation

  • Ewelina Krzywinska & Chahrazade Kantari-Mimoun & Yann Kerdiles & Michal Sobecki & Takayuki Isagawa & Dagmar Gotthardt & Magali Castells & Johannes Haubold & Corinne Millien & Thomas Viel & Bertrand Ta, 2017. "Loss of HIF-1α in natural killer cells inhibits tumour growth by stimulating non-productive angiogenesis," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01599-w
    DOI: 10.1038/s41467-017-01599-w
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    Cited by:

    1. Isaac Dean & Colin Y. C. Lee & Zewen K. Tuong & Zhi Li & Christopher A. Tibbitt & Claire Willis & Fabrina Gaspal & Bethany C. Kennedy & Veronika Matei-Rascu & Rémi Fiancette & Caroline Nordenvall & Ul, 2024. "Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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