Exercise-induced modulation of monocytes in breast cancer survivors

Abstract

Background Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. Objectives The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. Methods Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14 + CD16 - and CD14 + CD16 + monocytes using flow cytometry. Results Exercise training decreased IL-1ß + CD14 + CD16 - proportion (24.6%, p=0.016), IL-1ß + CD14 + CD16 - mean fluorescence intensity (MFI) (−9989, p=0.014), IL-1ß + CD14 + CD16 + MFI (−11101, p=0.02), and IL-6 + CD14 + CD16 - proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14 + CD16 - (−63, p=0.002) and CD14 + CD16 + (−18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14 + CD16 + concentrations being decreased at 1 h post without changes in intracellular cytokine production. Conclusions Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors

“…The study design and methods have been described in detail previously and consisted of mostly the same women in our previous studies ( 16 , 18 , 19 , 25 , 26 ). Briefly, all participants were physically inactive and a sub-set from a more extensive investigation (NCT03760536).…”

“…After training, follow-up testing (Final) for BCS was the same as Base. Testing visits included a preliminary assessment and familiarization, maximal cardiopulmonary exercise testing and body composition, and an acute bout of exercise at 60% of peak power with blood taken before exercise (Pre), immediately following completion of exercise (Post) and 1 hour after exercise completion (1Hr Post) ( 25 , 26 ). Table 1 shows the BCS exercise training prescription and their adherence and compliance to the program with this sub-study utilizing additional participants from our previous publications.…”

“…Exercise training consisted of 3 x 1-hour semi-supervised sessions/week for 16 weeks at the “Get REAL and HEEL Breast Cancer Rehabilitation Facility” ( 25 ). Table 1 shows that of the prescribed 48 sessions, participants attended 35.6 ± 10.6 days (74.2 ± 22.0%).…”

“…The acute exercise immune response in healthy adults is well characterized for major leukocyte subsets ( 8 , 22 ), and there are a growing number of acute exercise studies in BCS ( 23 , 24 ). For the first time that we are aware of, we have recently described in BCS the acute exercise-mediated monocyte ( 25 ) and mucosal-associated invariant T-cell (MAIT) ( 26 ) responses before and after 16 weeks of exercise training. Our results suggest that the acute response was beneficially modulated following 16 weeks of exercise training.…”

The Influence of Modifiable Factors on Breast and Prostate Cancer Risk and Disease Progression

“…Thus, lifestyle interventions such as physical exercise, may improve the inflammatory state of all patients ( Khosravi et al, 2019 ). While the exact mechanisms are not fully understood, one hypothesis is that exercise reduces monocyte cytokine production ( Khosravi et al, 2021 ).…”