Background Exercise enhances immunosurveillance and prevents development and recurrence of a variety of cancer types. 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. The mechanisms underlying the clinical benefits of exercise in cancer patients are still unclear. Substantial aspects like antigen specificity of exercise-mobilized T cells or secreted markers have only recently attracted research attention. This study aims to comprehensively understand the characteristics of exercise-mediated T cells at a mechanistic level and therefore lay the foundation to optimize exercise effects in cancer patients.

Methods 23 healthy participants enrolled in our INHALE study 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 the cohort was 37 years, the mean BMI 23.37 kg/m2 and the physical activity level 3585 MET-min/wk, as assessed by IPAQ-SF. The participants completed the high-intensity (HIIT) exercise session at a mean of 96.4% of their maximal heart rate and 118.1% of the maximal power on the VO2 max test, respectively. A strong mobilization of natural killer (NK) and T cells was observed at ex02. All cell subsets fell below baseline counts at ex60. Exercise-mobilized CD8+ T cells exhibited a higher proportion of 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. The strongest correlation with CD8+ T cell mobilization was found with catecholamine levels, and to a lesser extent with proteins linked to chemotaxis and cytolysis. To assess the T cell specificity dynamics against a panel of common viral epitopes following high-intensity exercise, a DNA-barcoded peptide-MHC multimer assay was conducted. In the context of the most prevalent specificities EBV, HHV-6B, and SARS-CoV-2, virus peptide-specific CD8+ T cells are mobilized by HIIT and markedly egress peripheral blood. This egress may occur to peripheral tissues, where the cells increase immunosurveillance.

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. Additionally, 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.

Acknowledgements This work is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – project number 505368854.

Trial Registration The study is registered under NCT05826496.

Ethics Approval Capital Region’s Ethics Committee approval H-23006672.

Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.