Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

Abstract

Background: Reduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls.

Methods: Age-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise.

Results: At 0 h, conventional T cell counts increased by 45%-64% with no differences between groups. T cell frequency decreased by -3.5% for CD3⁺ and -4.5% for CD4⁺ cells relative to base at 0 h with CD8⁺ cells experiencing a delayed decrease of -4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8⁺CD57⁺ cells was -18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8⁺perforin⁺ GMFI. CD3⁺Vα7.2⁺CD161⁺ counts, but not frequencies, increased by 69% post-exercise while CD3⁺CD56⁺ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h.

Conclusion: Following acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8⁺ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined.

Keywords: androgen deprivation therapy (ADT); conventional t cells (Tconv); exercise immunology; exercise induced immunosuppression; exercise oncology; unconventional t cells.