Natural killer (NK) cells, which are found in the blood, are crucial in the prevention and treatment of cancer. They function by eliminating malignant tumors in an innate immune manner. NK cells express an array of activating and inhibitory receptors that recognize cancer cells without the need for immunization. Cytotoxicity is a process that results in damaging or destroying cells. The antitumor cytotoxicity of NK cells depends on their ability to recognize cancer cells and produce cytotoxic proteins. Mitochondrial bioenergetics is essential for optimizing NK cell effector functions, including increased cytotoxic potential and cytokine production.
Regular exercise reduces mortality associated with most cancers. An acute bout of exercise mobilizes NK cells that enter the bloodstream from peripheral tissues; it can modulate the antitumor cytotoxicity of NK cells by altering cellular protein contents in an intensity-dependent manner. However, patients with malignancies experience gradual declines in muscle strength and cardiorespiratory fitness, which can influence their ability to exercise. This may lead to a more sedentary lifestyle. High-intensity interval training (HIIT) has been shown to be a more effective modality for improving cardiorespiratory fitness than moderate-intensity continuous training in both healthy individuals and patients with cardiovascular disease.
Our study, published in the May issue of Medicine & Science in Sport & Exercise®, involved 60 sedentary males who were randomly assigned to engage in either HIIT or moderate-intensity continuous training, or were assigned to a control group that did not receive exercise intervention. We observed that HIIT was superior to moderate-intensity training for enhancing exercise performance by increasing peak pulmonary ventilation and work-rate. Notably, both types of exercise training improved two cytotoxic characteristics of NK cells that involved the increases in cytotoxic proteins expressions and proliferative capacity of NK cells in the blood. Moreover, the two exercise regimens effectively elevated membrane potential and depressed cell matrix oxidant burden in the mitochondria of NK cells. This was associated with an increased oxygen uptake efficiency in NK cells.
NK cells are also important antiviral white blood cells that can rapidly respond to pathogens before an adaptive immune response occurs. Clinical studies in patients with COVID-19 have shown decreased NK numbers and function, resulting in decreased clearance of infected cells and increased tissue inflammation. Our previous and present studies indicate that moderate-intensity exercise training downregulated the senescent and inhibitory receptors on NK cells, thereby increasing clonal expansion and simultaneously improving NK cells’ ability to recognize and take cytotoxic action against viruses and cancer cells.
Our experimental findings could help determine effective exercise regimens for simultaneously improving cardiorespiratory fitness and the bioenergetic efficiency of NK cells in people living a sedentary lifestyle.
Jong-Shyan Wang, PhD, is a professor at the Graduate Institute of Rehabilitation Science at Chang Gung University, Taiwan. Dr. Wang was included in Stanford University Names World’s Top 2% of Scientists in 2021. His research focuses on developing exercise prescriptions for inflammatory/immunity, thrombotic and cardiovascular disorders.
Disclosure: This work was supported by the National Science Council of Taiwan and the Chang Gung Medical Research Program.
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