T-cell Response To Exercise Training Among Women At Heightened Risk Of Breast Cancer.

Abstract

Aging causes changes in the peripheral T-cell compartment that may increase susceptibility to cancer and lower immune responses. Fitness is associated with lower frequencies of highly differentiated T-cells, increased naïve T-cells, and elevations in myokines such as IL-7 that contribute to naïve T-cell output, indicating that exercise may help preserve immunity. PURPOSE: Examine the impact of exercise training on the differentiation status of CD4+ and CD8+ T-cells, recent thymic emigrants (RTE), and plasma levels of IL-7 in older women with an elevated risk of breast cancer (obesity status, postmenopausal, elevated Gail and/or lifetime risk score or history of non-invasive breast cancer). METHODS: 44 women (VO2=19.58±3.37 ml/kg/min) were randomized to: high-intensity interval training (HIIT; n=16; 63.73±6.86yrs); moderate continuous exercise (MCE; n=14.; 64.62±12.21yrs); or control (CNT; n=14; 63.35±6.99yrs). Participants completed clinically supervised treadmill exercise 3x/week for 12 weeks using heart rate training. Naive (NA), central memory (CM), effector memory (EM) and CD45RA+ effector memory (EMRA) CD4+ and CD8+ T-cells, and RTE (CD4NA or CD8NA CD31+CD103+) in blood were quantified before and after training. Fold changes (cells/μl) were calculated by (post-pre)/pre and compared across groups via ANOVA with p<0.05 considered significant. RESULTS: 11, 10, and 11 participants completed the HIIT, MCE, and CNT training, respectively. Compared to HIIT, MCE increased total lymphocytes (-0.05±0.13 vs. 0.12±0.12), CD4 (-0.29±0.24 vs. 0.21±0.30), CD4 CM (-0.23±0.20 vs. 0.36±0.27), CD4NA (-0.33±0.32 vs. 0.31±0.39), and CD8EM (-0.16±0.31 vs. 0.32±0.31). The change in number of CD4CM was higher in MCE compared to CNT (0.36±0.27 vs. -0.24±0.42). No changes were found for IL-7 or RTEs. CONCLUSION: Immune responses to exercise training in women with an elevated risk of breast cancer are likely to vary depending on the intensity of exercise. Future research should focus on investigating the potential that exercise may have on T-cell phenotypes and their relation to breast cancer risk. Funded by NCI R25 CA057730, the MD Anderson Cancer Center/Energy Balance Assessment Supplemental Funding, MD Anderson Cancer Center, Center for Energy Balance in Cancer Prevention and Survivorship, UA T32CA009213.