Journal Article

Impact of exercise training on tumour‐infiltrating T cells in human prostate cancer: A secondary analysis of a randomized controlled trial (PRO‐TEST)

Hasselager, Thomas, Toft, Birgitte Grønkær, Brasso, Klaus, Jakobsen, Henrik, Thomsen, Simon Nørskov, Røder, Andreas, Wriedt, Emil, Lehrskov, Louise Lang, Simonsen, Casper, Djurhuus, Sissal Sigmundsdottir, Christensen, Jesper Frank, Wielsøe, Sabrina, Stærk, Marianne Gardar, Østergren, Peter Busch

2025

Overview

Exercise training reduces tumour growth by increasing tumour‐infiltrating T‐cell density in preclinical models. However, it remains unknown whether exercise training can modify intratumoural T cells in humans.The aim of this study was to compare the effects of an exercise training intervention versus control on human prostate intratumoural T‐cell density.This study is a secondary analysis of a randomized controlled trial. We randomly allocated men (age > 18 years) with treatment‐naive localized prostate cancer scheduled for radical prostatectomy 2:1 to exercise training intervention or control. The exercise intervention consisted of supervised, high‐intensity interval bicycling four times per week from the time of randomization until prostatectomy. Intratumoural CD3 + and CD8 + T‐cell densities in diagnostic biopsies and postsurgical prostatectomy specimens were quantified using immunohistochemistry. Between‐group differences in changes from baseline to follow‐up were estimated using constrained baseline linear mixed‐effect models.A total of 30 participants were included (exercise intervention, n  = 20; control, n  = 10). We found no between‐group differences in changes in CD3 + T cells [mean difference (95% confidence interval): −17 (−185; 150) cells/mm 2 ] or CD8 + T cells [mean difference (95% confidence interval): −16 (−206; 172) cells/mm 2 ]. Additionally, we found no statistically significant correlations between changes in T‐cell density and the number of exercise training sessions attended or changes in maximal oxygen consumption.In this secondary analysis of a randomized controlled trial, we found no impact of the exercise regimen on tumour‐infiltrating CD3 + and CD8 + T‐cell density in human prostate cancer. What is the central question of this study? Does exercise training increase human prostate intratumoural T‐cell density? What is the main finding and its importance? In this randomized controlled trial, we found no impact of the exercise training regimen on CD3 + and CD8 + T‐cell density. Although this suggests that exercise training might not modify intratumoural T‐cell composition in prostate cancer, important methodological challenges might limit the interpretation of our data. More studies are needed to evaluate the capacity of exercise training to modify human intratumoural immune cell composition.