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Exercise suppresses tumor growth through epinephrine- and IL-6-dependent mobilization and redistribution of NK cells
  1. Line Pedersen1,
  2. Manja Idorn2,
  3. Gitte Holmen Olofsson2,
  4. Intawat Nookaew3,
  5. Rasmus Hvass Hansen4,
  6. Helle Hjorth Johannesen4,
  7. Jürgen C Becker5,
  8. Britt Lauenborg1,
  9. Katrine S Pedersen1,
  10. Christine Dethlefsen1,
  11. Jens B Nielsen6,
  12. Julie Gehl7,
  13. Bente Klarlund Pedersen1,
  14. Per thor Straten8 and
  15. Pernille Hojman1
  1. Aff1 grid.475435.4Centre of Inflammation and Metabolism and Centre of Physical Activity ResearchRigshospitalet, Faculty of Health Science, University of Copehagen Copenhagen Denmark
  2. Aff2 grid.4973.90000000406467373Centre for Cancer Immune Therapy, Dept. of HematologyCopenhagen University Hospital Herlev Denmark
  3. Aff3 grid.135519.a0000000404462659Dept. of Chemical and Biological Engineering, Chalmers University of TechnologyGöteborg, Sweden and Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 Göteborg Sweden USA
  4. Aff4 grid.4973.90000000406467373Dept. of RadiologyUniversity Hospital Copenhagen Herlev Denmark
  5. Aff5 grid.410718.b0000000102627331Dept. for Translational Skin Cancer Research (TSCR) within the German Cancer Consortium (DKTK)Westdeutsches Tumorzentrum, University Hospital Essen Essen Germany
  6. Aff6 grid.5371.00000000107756028Dept. of Chemical and Biological EngineeringChalmers University of Technology Göteborg Sweden
  7. Aff7 grid.411900.d0000000406468325Dept. of OncologyCopenhagen University Hospital, Herlev Denmark Herlev Denmark
  8. Aff8 grid.411900.d0000000406468325Centre for Cancer Immune Therapy (CCIT)Copenhagen University Hospital Herlev Herlev Denmark

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Meeting abstracts

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.