elife-59996-v1 (3).pdf (2.99 MB)
Cytotoxic T-cells mediate exercise-induced reductions in tumor growth.
journal contributionposted on 2020-10-30, 12:17 authored by Helene Rundqvist, Pedro Veliça, Laura Barbieri, Paulo A Gameiro, David Bargiela, Milos Gojkovic, Sara Mijwel, Stefan Markus Reitzner, David Wulliman, Emil Ahlstedt, Jernej Ule, Arne Östman, Randall S Johnson
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.
Crick (Grant ID: 10002, Grant title: Ule FC001002)