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.
Keywords: cancer biology; exercise; human; immunology; immunotherapy; inflammation; metabolism; mouse.
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. However, it is still unknown how exercise exerts its protective effects. One of the hallmarks of cancer is the ability of cancer cells to evade detection by the immune system, which can in some cases stop the body from eliminating tumor cells. Rundqvist et al. used mice to investigate how exercise helps the immune system act against tumor progression. They found that when mice exercised, tumor growth was reduced, and this decrease in growth depended on the levels of a specific type of immune cell, the CD8+ T cell, circulating in the blood. Additionally, Rundqvist et al. found that CD8+ T cells were made more effective by molecules that muscles released into the blood during exercise. Isolating immune cells after intense exercise showed that these super-effective CD8+ T cells alter how they use molecules for energy production after exertion. Next, 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. The ability of T cells to identify and eliminate cancer cells is essential to avoid tumor growth, and is one of the foundations of current immune therapy treatments. Exercise could improve the outcome of these treatments by increasing the activation of the immune system, making tumor-fighting cells more effective.
© 2020, Rundqvist et al.