INTRODUCTION: Physical activity improves immune competency and is associated with a lower rate of cancer recurrence in colorectal cancer survivors. However, the exact mechanisms underlying these improvements remain unclear. Exercise-derived cytokines (exerkines), particularly IL-7 and IL-15, are crucial in maintaining optimal immune health. This study investigated whether a 12-week structured exercise training intervention increases IL-7 and IL-15 in colorectal cancer survivors. METHODS: Sixty colorectal cancer survivors were randomized to a moderate-intensity home-based aerobic exercise group (150 min/week) or a control group for 12 weeks. IL-7 and IL-15 were quantified using ELISA, and body composition was measured using dual-energy x-ray absorptiometry. RESULTS: At baseline, participants treated with chemotherapy had lower IL-7 than those not treated with chemotherapy (-3.3 pg/ml (95% CI -1.3 to -5.4); p = 0.002). Baseline fitness capacity correlated with IL-15 (r -0.37; p = 0.004). IL-7 increased in the exercise group (2.3 pg/ml (95% CI 0.9 to 3.8; p = 0.003)), but not in the control group (1.2 pg/ml (95% CI 0.3 to 2.8; p = 0.31)). IL-15 did not differ between groups. Longitudinal changes in IL-15 were associated with changes in body composition. DISCUSSION: Aerobic exercise may improve immune function in colorectal cancer survivors by restoring IL-7 after chemotherapy and improving IL-15 by altering body composition. CLINICAL TRIAL REGISTRATION: (https://clinicaltrials.gov/study/NCT03975491), identifier (NCT03975491).

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