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

TY - JOUR

T1 - Cytotoxic t-cells mediate exercise-induced reductions in tumor growth

AU - Rundqvist, Helene

AU - Veliça, Pedro

AU - Barbieri, Laura

AU - Gameiro, Paulo A.

AU - Bargiela, David

AU - Gojkovic, Milos

AU - Mijwel, Sara

AU - Reitzner, Stefan Markus

AU - Wulliman, David

AU - Ahlstedt, Emil

AU - Ule, Jernej

AU - Östman, Arne

AU - Johnson, Randall S.

N1 - Funding Information: Carolin Lindholm and Andrea Berk (Karolinska Institutet) for expertise in immunohistochemistry, Prof. Kristian Pietras (Lunds Universitet) for sharing the MMTV-PyMT mouse strain on the FVB background, Dr. Carina Strell (Karolinska Institutet) for sharing the I3TC cell line, and Prof. Ananda Gold-rath and Prof. Christer Höög for discussions. Metabolomics experiments were performed at the Swedish Metabolomics Center (Umeå, Sweden) and on the Precision Metabolomics platform at Metabolon Inc (Morrisville, NC, US). [U-13C6]glucose metabolomics experiments were performed in the Metabolomics STP at The Francis Crick Institute (London, UK), which receives its core funding from Cancer Research UK (FC001999), the UK Medical Research Council (FC001999), and the Wellcome Trust (FC001999). The work was funded by the Knut and Alice Wallenberg Scholar Award, the Swedish Medical Research Council (Vetenskapsrådet), the Swedish Cancer Fund (Cancerfonden), the Swedish Children’s Cancer Fund (Barncancerfonden), the Swedish Society of Medicine (Svenska läkaresällskapet) and a Principal Research Fellowship (214283/Z/18/Z) to RSJ from the Wellcome Trust. We thank James MacRae and James Ellis for help with the GC-MS analysis. Funding Information: Carolin Lindholm and Andrea Berk (Karolinska Institutet) for expertise in immunohistochemistry, Prof. Kristian Pietras (Lunds Universitet) for sharing the MMTV-PyMT mouse strain on the FVB back-ground, Dr. Carina Strell (Karolinska Institutet) for sharing the I3TC cell line, and Prof. Ananda Gold-rath and Prof. Christer Höög for discussions. Metabolomics experiments were performed at the Swedish Metabolomics Center (Umeå, Sweden) and on the Precision Metabolomics platform at Metabolon Inc (Morrisville, NC, US). [U-13 C6 ]glucose metabolomics experiments were performed in the Metabolomics STP at The Francis Crick Institute (London, UK), which receives its core funding from Cancer Research UK (FC001999), the UK Medical Research Council (FC001999), and the Wellcome Trust (FC001999). The work was funded by the Knut and Alice Wallenberg Scholar Award, the Swedish Medical Research Council (Vetenskapsrådet), the Swedish Cancer Fund (Cancerfonden), the Swedish Children’s Cancer Fund (Barncancerfonden), the Swedish Society of Medicine (Svenska läkaresällskapet) and a Principal Research Fellowship (214283/Z/18/Z) to RSJ from the Wellcome Trust. We thank James MacRae and James Ellis for help with the GC-MS analysis. Publisher Copyright: © Rundqvist et al.

PY - 2020/10

Y1 - 2020/10

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85094684302

U2 - 10.7554/eLife.59996

DO - 10.7554/eLife.59996

M3 - Article

C2 - 33095157

AN - SCOPUS:85094684302

SN - 2050-084X

VL - 9

SP - 1

EP - 25

JO - eLife

JF - eLife

M1 - e59996

ER -