Background Exercise enhances immune surveillance and prevents the development and recurrence of several cancers. It has been well studied that acute exercise induces mobilization of lymphocytes into the peripheral blood, predominantly comprising of NK cells and antigen-experienced T cells.¹ However, the mechanisms underlying these clinical benefits are still unclear. The antigen specificity of exercise-mobilized T cells,² and the associated secreted markers have only recently attracted research attention.^{3 4} Thus, this study aims to comprehensively understand the characteristics of exercise-mobilized T cells at a mechanistic level, which is highly needed to optimize the effects of exercise in cancer patients.

Materials and Methods 23 healthy participants enrolled in our INHALE study (NCT05826496, Capital Region’s Ethics Committee approval H-23006672) underwent a single session of supervised high-intensity exercise on bicycle ergometers in May 2023, with peripheral blood samples collected before exercise (bsl), at 2 minutes post-exercise (ex02), and 60 minutes post-exercise (ex60).

Results The mean age of our cohort was 37 years, with a mean BMI of 23,37 kg/m² and a physical activity level of 3585 MET-min/wk assessed by IPAQ-SF. The participants completed the high-intensity exercise session at a mean of 96,4% of their maximal heart rate and 118,1% of the maximal power on VO₂ max test, respectively. We observe a strong mobilization of NK, T and B cells at ex02, which correlates strongly with adrenaline levels. All cell subsets fall below baseline counts at ex60. Exercise-mobilized CD8⁺ T cells show a higher proportion effector memory and terminally differentiated effector memory (TEMRA) T cells, in line with higher frequencies of CD57⁺, CD95⁺ and PD-1⁺ CD8⁺ T cells post-exercise. To assess the dynamics of T cell specificity against a panel of common viral epitopes following high-intensity exercise, we conducted a DNA-barcoded peptide-MHC multimer assay; the data will be presented at ITOC 2024.

Conclusions The INHALE study provides valuable data from a relatively large cohort of 23 healthy participants on the effects of exercise specifically in the T cell compartment. In addition, this investigation serves as an important physiological reference for our ongoing clinical exercise study in NSCLC patients (HI AIM). Prospectively, understanding exercise-triggered circulating tumor-associated antigen-specific T cells may be used to enhance the anti-tumor immune response. This work is funded by the German Research Foundation (DFG) - project number 505368854.

References

1. Gabriel H, Schwarz L, Born P, Kindermann W. Differential mobilization of leucocyte and lymphocyte subpopulations into the circulation during endurance exercise. Eur J Appl Physiol Occup Physiol. 1992;65(6):529–34.

2. Kunz HE, Spielmann G, Agha NH, O’Connor DP, Bollard CM, Simpson RJ. A single exercise bout augments adenovirus-specific T-cell mobilization and function. Physiol Behav. 2018 Oct 1;194:56–65.

3. Kurz E, Hirsch CA, Dalton T, Shadaloey SA, Khodadadi-Jamayran A, Miller G, et al. Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer. Cancer Cell 2022 Jul 11;40(7):720–737.e5.

4. Monje M, Borniger JC, D’Silva NJ, Deneen B, Dirks PB, Fattahi F, et al. Roadmap for the emerging field of cancer neuroscience. Cell 2020;181(2):219–22.

References K. Leuchte: None. V. Luu: None. S. Salo: None. A. Vinther: None. P. thor Straten: None. G. Olofsson: None.