Exercise Training and Immune Crosstalk in the Breast Cancer Microenvironment:
Exploring the Paradigms of Exercise-Induced Immune Modulation and Exercise-Induced
Myokines.
Jorming Goh, Ph.D.1, *, Negin Niksirat2, Kristin L. Campbell, Ph.D.2, 3
*Corresponding
Author. Address: Human Performance Laboratory,
Defence Medical & Environmental Research Institute, DSO National
Laboratories, 27 Medical Drive, Republic of Singapore (117510).
Email address: GJorMing@dso.org.sg
Tel: 65-6485-7122
1Human
Performance Laboratory, Defence Medical and Environmental
Research Institute, DSO National Laboratories, Republic of Singapore.
2Rehabilitation
Sciences, University of British Columbia, Vancouver B.C.,
Canada.
3Cancer
Prevention Center, University of British Columbia, Vancouver
B.C., Canada.
Abstract
The benefits of aerobic exercise as part of supportive care for breast cancer
therapy are well established. However, observational research suggests that
exercise may also play a role in reducing the risk of breast cancer and improve
treatment outcomes. One proposed mechanism for the protective effect of
aerobic exercise related to cancer risk and cancer outcomes that has not been
examined definitively, is the mechanism that mediate immune responses to
aerobic exercise. Two prevailing paradigms are proposed. The first paradigm
considers the host immune response as modifiable by aerobic exercise training.
This exercise-modulated immune-tumor crosstalk in the mammary
microenvironment may then alter the balance between tumor initiation and
progression versus tumor suppression. The second paradigm considers the
beneficial role of exercise-induced, skeletal muscle-derived cytokines, termed
“myokines”. These myokines exert endocrine-like effects on multiple organs,
including the mammary glands. To date, a comprehensive review of this topic is
not available, specifically focused on either: i) the immunomodulatory effects of
exercise in the breast cancer microenvironment or ii) the effects of exerciseproduced myokines and their effects on the mammary gland.
The objectives of this review are to: i) define the role of macrophages and T-cells
in breast cancer initiation and progression; ii) address the two paradigms that
support exercise-induced immunomodulation; iii) systematically assess the
literature for exercise intervention that assessed biomarkers relevant to both
paradigms in human intervention trials of aerobic exercise training, in healthy
women and women with breast cancer; incorporate pre-clinical animal studies
and non-RCTs for background discussion of putative mechanisms, through which
aerobic exercise training modulates the immunological crosstalk, or the myokinetumor interaction in the tumor microenvironment; and v) speculate on the
potential biomarkers and mechanisms that define an exercise-induced, antitumor “signature”, with a view toward developing relevant biomarkers for future
aerobic exercise intervention trials.
Key
Words:
Exercise,
breast
cancer,
immune,
myokines,
microenvironment, clinical trials, translational, immunotherapy.