Exercise-Dependent Regulation of NK Cells in Cancer Protection

Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently, exercise-dependent mobilization of NK cells was found to play a central role in exercise-mediated protection against cancer. Here, we review the link between exercise and NK cell function, focusing on circulating exercise factors and additional effects, including vascularization, hypoxia, and body temperature in mediating the effects on NK cell functionality. Exercise-dependent mobilization and activation of NK cells provides a mechanistic explanation for the protective effect of exercise on cancer, and we propose that exercise represents a potential strategy as adjuvant therapy in cancer, by improving NK cell recruitment and infiltration in solid tumors.

TrendsExercise controls tumor growth through epinephrine-dependent mobilization of NK cells, stressing the importance of intensity driven exercise in tumor control.Muscle-derived exercise factors, known as myokines, can regulate NK cell proliferation, maturation, and activation, representing a muscle-to-immune cell crosstalk axis during exercise.Exercise promotes additional effects within tumors, including improved vascularization and perfusion, resolution of hypoxia, and increased body temperature, all contributing to a microenvironment that promotes NK cell responsiveness.Exercise is being increasingly prescribed to cancer patients to mitigate treatment-related side effects, as well as to improve quality of life and physical functioning. Yet, the cumulative effects of exercise may translate into both improved tumor control and enhanced treatment efficacy.