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.

Figure 1

Gating strategy used to identify conventional and unconventional T cells. Conventional T cells were identified using (A) lymphocytes, (B) followed by CD3⁺ cells (C) before being subdivided using CD4⁺ and CD8⁺. Within the CD8⁺ population, histograms were created for (D) CD57 and (E) perforin. Mucosal Associated Invariant T (MAIT) cells were identified using (F) lymphocytes, (G) CD3⁺, and (H) Vα7.2⁺ and CD161⁺ cells. (I) MAIT cells were then subdivided using CD4 and CD8. Natural killer (NK)-like T cells were identified using (J) lymphocytes, (K) then CD3⁺CD56⁺ cells, and histograms were created for (L) perforin and (M) CD57.

Figure 2

Changes in conventional T cell populations at baseline (base) and during recovery from acute aerobic exercise. Cell counts are reported for (A) CD3⁺, (B) CD3⁺CD4⁺, and (C) CD3⁺CD8⁺ T cells. Cell frequencies reported for (D) CD3⁺, (E) CD3⁺CD4⁺, and (F) CD3⁺CD8⁺ T cells Data are reported as mean and standard deviation. *, **, *** P < 0.05, P < 0.01, P < 0.001 vs. Baseline.

Figure 3

Changes in unconventional T cell populations at baseline (base) and during recovery from acute aerobic exercise. Cell counts are reported for (A) CD3⁺Vα7.2⁺CD161⁺ Mucosal Associated Invariant T (MAIT) cells, (B) CD3⁺Vα7.2⁺CD161⁺CD8⁺ MAIT cells, and (C) CD3⁺CD56⁺ Natural killer (NK)-like T cells. Cell frequencies are reported for (D) CD3⁺Vα7.2⁺CD161⁺ MAIT cells, (E) CD3⁺Vα7.2⁺CD161⁺CD8⁺ MAIT cells, and (F) CD3⁺CD56⁺ NKT-like cells. Data are reported as mean and standard deviation. *, **, *** P < 0.05, P < 0.01, P < 0.001 vs. Baseline.