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

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Graduate College

Grantor dc:publisher

The University of Arizona.

Year dc:date.issued

2023

Author dc:creator

• Smith, Kyle Andrew

Advisor dc:contributor.advisor

• Simpson, Richard

Committee members dc:contributor.committeemember

• Katsanis, Emmanuel
• Lynch, Ron
• Konhilas, John
• Lybarger, Lonnie

Statement dc:rights

• Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10150/668240

OAI identifier oai:identifier

oai:repository.arizona.edu:10150/668240