Changes in circulating immune cells and cytokines after high-intensity aerobic exercise in patients with prostate cancer undergoing active surveillance from the ERASE randomized controlled trial

Background – Exercise can modulate immune function and inflammatory signaling in cancer populations; however, its effects on the immune system in men with localized prostate cancer undergoing active surveillance are unknown. This study examined the effects of high-intensity interval training (HIIT) on circulating immune cell phenotypes, function, and systemic cytokine levels in this clinical setting. Methods – This was a secondary analysis of the Exercise During Active Surveillance for Prostate Cancer (ERASE) trial, a single-center randomized controlled trial. Fifty-two men with localized prostate cancer on active surveillance were randomized to a 12-week supervised aerobic HIIT program (n=26) or usual care (n=26). HIIT consisted of three sessions per week at 85% to 95% of peak oxygen consumption. Fasting blood samples were collected at baseline and post-intervention. Changes in immune cell subsets (T cells, B cells, and NK cells; flow cytometry), NK cell cytotoxicity, and plasma cytokine concentrations were assessed. Analyses of covariance were used to compare between-group differences. Results – The HIIT group attended 96% of prescribed sessions. Compared with usual care, the HIIT group showed a significant increase in the proportion of the circulating major NK-cell subset (CD3−CD56+CD16+) (adjusted between-group difference, 2.0%; 95% CI, 0.3 to 3.7; p=0.024) and PBMC-mediated cytotoxicity against K562 (2.9%; 95% CI, 0.3 to 5.4; p=0.031). A significant between-group decrease was also observed in basophil counts (-0.04 ×109/L; 95% CI, -0.07 to -0.01; p = 0.011), with no differences in other leukocyte populations. HIIT significantly reduced plasma levels of IL-4 (-0.02 pg/mL; 95% CI, -0.03 to -0.01; p = 0.011) and IL-12p70 (-0.14 pg/mL; 95% CI, -0.23 to -0.06; p = 0.002) compared with usual care. No significant between-group differences were observed in T cell or B cell subsets, or other inflammatory cytokines including IL-6 and TNF-α. Conclusions – A 12-week supervised HIIT program significantly increased the proportion of the circulating major NK-cell subset and PBMC-mediated cytotoxicity while reducing IL-4 and IL-12p70 concentrations in men with prostate cancer undergoing active surveillance. Because these were peripheral-blood measures rather than tumor-level readouts, and given the exploratory design and number of comparisons, these findings should be interpreted as hypothesis-generating and require confirmation in larger, adequately powered studies.