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.
Highlights
In humans, exercising cohorts have lower rates of cancer incidence (Moore et al, 2016) and better outcomes across a range of cancer diagnoses (Cormie et al, 2017; Friedenreich et al, 2016), proportionate to the degree and intensity of exercise
Immune cells from mice that had exercised frequently were transferred into mice that had not exercised, where they were more effective against tumor cells than the immune cells from untrained mice. These results demonstrate that CD8+ T cells are altered by exercise to improve their effectiveness against tumors
We found that exercise itself can modify cytotoxic T-cell metabolism, and that exercise-induced effects on tumor growth are dependent on cytotoxic T-cell activity
Summary
In humans, exercising cohorts have lower rates of cancer incidence (Moore et al, 2016) and better outcomes across a range of cancer diagnoses (Cormie et al, 2017; Friedenreich et al, 2016), proportionate to the degree and intensity of exercise. Cancer Biology Immunology and Inflammation eLife digest Exercise affects almost all tissues in the body, and scientists have found that being physically active can reduce the risk of several types of cancer as well as improving outcomes for cancer patients. It is still unknown how exercise exerts its protective effects. We found that exercise itself can modify cytotoxic T-cell metabolism, and that exercise-induced effects on tumor growth are dependent on cytotoxic T-cell activity
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