Adrenergic Mobilization of the Immune System and the Anti-Cancer Effects of Exercise

Abstract

A single bout of exercise has a profound effect on the number and composition of immune cells within the circulation. Within this response, there exists a preferential mobilization of effector lymphocytes with cytotoxic potential, and evidence exists for an anti-tumor effect of exercise dependent upon NK-cells or CD8+ T-cells relative to the specific tumor model. We herein demonstrate that blockade of the β2-AR in humans during exercise significantly blunts the mobilization of lymphocytes, while β1-AR blockade or β1-AR blockade plus PDE4 inhibition significantly augment the mobilization of NK-cells or monocytes, γδ T-cells, and CD8 T-cells, respectively. We provide single cell transcriptomic data to further the understanding of signaling within immune cells during exercise, and demonstrate that isoproterenol infusion in humans mimics the mobilization of NK-cell phenotypes seen during exercise at 70% VO2max. Further, we demonstrate in various murine models of A20 lymphoma that exercise exerts a protective effect on tumor progression, and this effect is dependent upon both β2-AR signaling and NK-cells. We lastly demonstrate that exercising animals present with increased infiltration of cytotoxic lymphocyte populations within tumors, and that these infiltrates correlate with tumor kinetics.