Degree

Doctor of Philosophy (PhD)

Department

Kinesiology

Document Type

Dissertation

Abstract

Immunosenescence refers to the gradual decrease in immune competency over time, which is strongly associated with increased risk of cancer and a rise in morbidity and mortality among the elderly. Regular physical activity can be beneficial to the immune system by potentially decreasing the frequency of senescent immune cells and reducing mortality risk in cancer patients and survivors. However, less is known on the impact of acute exercise on “aggressive” cancers, such as hormone receptor negative breast cancers. Further, the mechanistic underpinnings of the exercise-associated improvements in the immune response to cancer remains unclear. In this context, past studies have suggested that acute bouts of exercise lead to a preferential mobilization of immune cells with potent anti-cancer effects in the peripheral blood compartment. In addition to promoting immune cell mobilization, it is likely that exercise also improves the functionality and metabolism of specific immune cells such as NK cells. As such, this dissertation aimed to investigate the effects of exercise on immune cell function and metabolism in sedentary individuals. The first chapter examined whether acute bouts of exercise and infection history with latent herpesviruses cytomegalovirus (CMV) impact the mobilization of distinct populations of Innate Lymphoid Cells (ILCs). This study, published in Viruses, showed that individual bouts of acute exercise mobilize traditionally tissue resident ILCs into the blood compartment. However, latent CMV infection history reduces the ingress of total ILC (tILC), and progenitor ILC (ILCP). The second chapter investigated the effects of exercise on Natural Killer (NK) cells bioenergetics and cytotoxic functions when NK cells are activated by aggressive breast cancer subtypes under hypoxic environment. This is the first study to show that a single acute bout of exercise recues the NK cell function lost due to hypoxic conditions. Further, activated NK cells by triple-negative breast cancer cells showed increased mitochondrial oxidative capacity and decreased Reactive Oxygen Species (ROS) following exercise, both known to being associated with improved and impaired functions respectively. Overall, this dissertation provides new insights into our understanding of NK cell function in response to exercise, playing a powerful role to enhance immunosurveillance and protect from cancer incidence.

Date

8-14-2022

Committee Chair

Spielmann, Guillaume

Available for download on Thursday, August 14, 2025

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