Author(s): POIRIER, L., PARENT-ROBERGE, H., FONTVIEILLE, A., PAVIC, M., FÜLÖP, T., TAI, L.H., RIESCO, E., Institution: UNIVERSITÉ DE SHERBROOKE, Country: CANADA, Abstract-ID: 1694

INTRODUCTION:
Exercise is increasingly recognized as an adjunct therapeutic strategy in oncology, accumulating evidence highlighting its potential to enhance anti-tumor immune function. Tumor-bearing animal studies have suggested that each aerobic exercise bout may acutely promote the infiltration of effector CD8+ cytotoxic T-cells (CTLs) in tumoral tissue and enhance the anti-tumor immune response. As the magnitude of this acute immune response is governed by exercise intensity, high-intensity interval exercise (HIIE) may represent a promising strategy to stimulate anti-cancer immunity in individuals living with cancer. Currently, the acute effects of moderate-intensity exercise (MOD) and HIIE on circulating T-cells has not been described in cancer patients receiving chemotherapy. Objective: To characterize the acute CTLs response to a MOD and a work-matched HIIE in metastatic cancer patients undergoing chemotherapy.
METHODS:
Eleven participants (45-65 years old) completed a block-randomized crossover trial including one MOD and one work-matched HIIE session. Blood samples were collected pre-exercise, immediately post-exercise and 1h post-exercise for peripheral blood mononuclear cells (PBMC) isolation. Total CTLs (CD3⁺CD8⁺) and differentiation subsets (naïve, central memory, effector memory [EM], and terminally differentiated effector memory T cells re-expressing CD45RA [TEMRA; CCR7⁻CD45RA⁺]) were identified. EM and TEMRA subsets were further phenotyped for their expression of CD28, PD-1, CD95, CXCR3 and CXCR4. Blood levels at each timepoint were computed using complete blood counts with leukocyte differentials, and post-exercise values were adjusted for exercise-induced changes in plasma volume.
RESULTS:
Total, CD28-, CD95+ and CXCR3+ TEMRA subsets increased immediately following both exercise conditions and returned to baseline levels 1h post-exercise (all p < 0.01). No statistically significant changes were observed in EM subsets, although a trend for post-exercise increase was noted in PD-1+ EM cells (q = 0.052). Significant changes in mean fluorescence intensity of these markers were detected in both EM and TEMRA cells, suggesting acute modulation of marker expression at the single cell level. Finally, no greater quantitative CTL mobilization was observed following HIIE compared with MOD when assessing quantitative changes in circulating cell numbers.
CONCLUSION:
In metastatic cancer patients undergoing chemotherapy, both MOD and work-matched HIIE induced a preferential mobilization and egress of CXCR3+ TEMRA cells, a phenotype associated with tissue-directed migration. These findings support the hypothesis that exercise may facilitate effector CTLs trafficking toward tumor tissue, a mechanism that remains to be confirmed in cancer patients and is currently being investigated in an ongoing trial (NCT06911970).