Cytotoxic T-cells mediate exercise-induced reductions in tumor growth

Author:

Rundqvist Helene12ORCID,Veliça Pedro1ORCID,Barbieri Laura13ORCID,Gameiro Paulo A4,Bargiela David15,Gojkovic Milos1,Mijwel Sara6ORCID,Reitzner Stefan Markus6ORCID,Wulliman David1ORCID,Ahlstedt Emil2,Ule Jernej4ORCID,Östman Arne7,Johnson Randall S15ORCID

Affiliation:

1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden

2. Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

3. Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padua, Italy

4. The Francis Crick Institute, London, United Kingdom

5. Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom

6. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

7. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

Abstract

Exercise has a wide range of systemic effects. In animal models, repeated exertion reduces malignant tumor progression, and clinically, exercise can improve outcome for cancer patients. The etiology of the effects of exercise on tumor progression are unclear, as are the cellular actors involved. We show here that in mice, exercise-induced reduction in tumor growth is dependent on CD8+ T cells, and that metabolites produced in skeletal muscle and excreted into plasma at high levels during exertion in both mice and humans enhance the effector profile of CD8+ T-cells. We found that activated murine CD8+ T cells alter their central carbon metabolism in response to exertion in vivo, and that immune cells from trained mice are more potent antitumor effector cells when transferred into tumor-bearing untrained animals. These data demonstrate that CD8+ T cells are metabolically altered by exercise in a manner that acts to improve their antitumoral efficacy.

Funder

Knut och Alice Wallenbergs Stiftelse

Vetenskapsrådet

Cancerfonden

Barncancerfonden

Svenska Läkaresällskapet

Cancer Research UK

Medical Research Council

Wellcome Trust

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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