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Exercise suppresses tumor growth through epinephrine- and IL-6-dependent mobilization and redistribution of NK cells

  • Line Pedersen1,
  • Manja Idorn2,
  • Gitte Holmen Olofsson2,
  • Intawat Nookaew3,
  • Rasmus Hvass Hansen4,
  • Helle Hjorth Johannesen4,
  • Jürgen C Becker5,
  • Britt Lauenborg1,
  • Katrine S Pedersen1,
  • Christine Dethlefsen1,
  • Jens B Nielsen6,
  • Julie Gehl7,
  • Bente Klarlund Pedersen1,
  • Per thor Straten8 and
  • Pernille Hojman1
Journal for ImmunoTherapy of Cancer20153(Suppl 2):P246

https://doi.org/10.1186/2051-1426-3-S2-P246

Published: 4 November 2015

Keywords

MelanomaEpinephrineLiver CancerTumor IncidenceLewis Lung

Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel running showed significant exercise related reduction in tumor incidence and growth across several tumor models including transplantable tumors (Lewis lung and B16 melanoma), chemically (diethylnitrosamine (DEN) induced liver cancer, and a model of spontaneous melanoma (Tg(Grm1)EPv transgenic mice). Microarray analysis revealed exercise-induced up-regulation of pathways associated with immune function, prompting further investigations. NK cell infiltration was significantly increased in tumors from exercising mice, and depletion of NK cells by anti-asialo-GM1 administration increased tumor growth and blunted the exercise-dependent tumor suppression. Mechanistic analyses showed that NK cells were engaged through an epinephrine-dependent mobilization, and blockade of this response by ß-adrenergic blockade blunted the exercise-dependent tumor inhibition. Moreover, exercise-induced IL-6 facilitated redistribution of NK cells to peripheral tissues and induced a shift towards more cytotoxic (CD11b-, CD27+) NK cells at the tumor site. Together these results link exercise, epinephrine and IL-6 to NK cell mobilization and activation, and ultimately to improved control of tumor growth.

Authors’ Affiliations

(1)
Centre of Inflammation and Metabolism and Centre of Physical Activity Research, Rigshospitalet, Faculty of Health Science, University of Copehagen, Copenhagen, Denmark
(2)
Centre for Cancer Immune Therapy, Dept. of Hematology, Copenhagen University Hospital, Herlev, Denmark
(3)
Dept. of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden and Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, Göteborg, USA
(4)
Dept. of Radiology, University Hospital Copenhagen, Herlev, Denmark
(5)
Dept. for Translational Skin Cancer Research (TSCR) within the German Cancer Consortium (DKTK), Westdeutsches Tumorzentrum, University Hospital Essen, Essen, Germany
(6)
Dept. of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden
(7)
Dept. of Oncology, Copenhagen University Hospital, Herlev, Denmark, Denmark
(8)
Centre for Cancer Immune Therapy (CCIT), Copenhagen University Hospital Herlev, Herlev, Denmark

Copyright

© Pedersen et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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