![]() ![]() To address this, we undertook studies of exercise-induced changes in tumor progression, and asked what metabolites are released in response to exercise as well as whether metabolites produced by exercise can alter cytotoxic T-cell function. In this study, we investigate the association between exercise, tumor growth, and CD8+ T-cell function. Exercise is known to affect immune cell function, and an altered immune response has been suggested as a mechanism underlying effects of exercise on cancer risk and progression ( Christensen et al., 2018). Many aspects of immune cell energetics are likely sensitive to the metabolic changes induced by exercise ( Henderson et al., 2004). ![]() The activity of immune cells is tightly linked with their metabolism ( O'Neill et al., 2016 Pearce and Pearce, 2013). Escape from immune control is a critical step toward progressive malignant growth in many cancers, and tumors achieve this in a number of ways, amongst them the dampening of antitumor T cell responses ( Dunn et al., 2002 Dunn et al., 2004 Beatty and Gladney, 2015 Zappasodi et al., 2018). By recognizing mutation-derived neoantigens, T cells can identify and eliminate malignant cells in a process known as immunosurveillance ( Dunn et al., 2002 Dunn et al., 2004). It is clear that cytotoxic T cells play a crucial role in controlling tumor growth. These shifts are reflected in systemic metabolite availability, which in turn modifies energy production throughout the body ( Henderson et al., 2004 Lezi et al., 2013 El Hayek et al., 2019). These exercise-induced alterations in metabolism change the ratios of energy substrates utilized, and can shift intramuscular metabolite profiles. The metabolic demands of strenuous physical exertion generally induce significant changes in nutrient utilization, principally via central carbon metabolism ( Brooks, 1998). ![]() The mechanisms underlying these observations have remained elusive, although recent work has indicated a relationship between immune response and exercise-induced changes in malignant progression ( Pedersen et al., 2016 Koelwyn et al., 2017). 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. Exercise could improve the outcome of these treatments by increasing the activation of the immune system, making tumor-fighting cells more effective. 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. ![]() These results demonstrate that CD8+ T cells are altered by exercise to improve their effectiveness against tumors. 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. Isolating immune cells after intense exercise showed that these super-effective CD8+ T cells alter how they use molecules for energy production after exertion. found that CD8+ T cells were made more effective by molecules that muscles released into the blood during exercise. 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. used mice to investigate how exercise helps the immune system act against tumor progression. 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. However, it is still unknown how exercise exerts its protective effects. 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. ![]()
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