The Impact of Aerobic Exercise on Circulating T-Cells and NK-Cells in Colorectal Cancer Survivors: A Secondary Analysis of a Randomized Trial
Eunhan Cho, Stephanie L. E. Compton, Shengping Yang, Mohamedtaki A. Tejani, Ahmed Zakari, Justin C. Brown, Guillaume SpielmannIntroduction
Aerobic exercise improves disease-free and overall survival in patients with colorectal cancer. This study tested the hypothesis that a key mechanism of action underpinning these survival benefits relates to exercise-induced improvements in inflammation and immunity in colorectal cancer survivors.
Methods
This trial randomized 60 survivors of stage I-III colorectal cancer to 12 weeks of home-based aerobic exercise or control. Endpoints included plasma sCD30, sGP130, IL-1β, and IL-2 measured using bead-based magnetic immunoassays, and the frequencies of circulating T-cell [CD4+ and CD8+ naïve, central memory, effector memory, and terminally differentiated effector memory (TEMRA)] and NK-cell subsets quantified by flow cytometry.
Results
Exercise training reduced sCD30 [−153.1 pg/mL (95% CI: −249.5, −56.7); p=0.014] but did not reduce sGP130, IL-1β, or IL-2 compared to control. Exercise training increased the proportions of resting NKG2D−/NKG2C+ NK-cells [2.75% (95% CI: 0.34, 5.15); p=0.03] and CD56+ bright KLRG1−/NKG2C+ NK-cells [4.46% (95% CI: 1.32, 7.60); p=0.006] compared to control. In the control group, sCD30 inversely correlated with naive CD8+ T-cells [r=−0.51 (95% CI: −0.82, 0.03); p=0.04], whereas sGP130 [r=0.46 (95% CI: −0.09, 0.72); p=0.01] and IL-2 positively correlated with CD8+ TEMRA frequencies [r=0.50 (95% CI: 0.06, 0.78); p=0.02]; these associations were not statistically significant in the exercise group.
Conclusion
In this secondary, exploratory analysis of a randomized trial, aerobic exercise reshaped aspects of the inflammatory-immune axis in colorectal cancer survivors. These findings refine our understanding of the biological mechanisms by which exercise may improve disease-free and overall survival in colon cancer survivors.