PO-378 Exercise-dependent regulation of immune cell function in a clinical cancer perspective

Abstract

IntroductionExercise is used as supportive therapy for cancer patients, aiming to improve patients’ physical functioning, quality-of-life and cancer-related fatigue. Emerging evidence suggests that exercise may also have direct anti-oncogenic effects on disease progression. Yet, in order to pursue ‘exercise as cancer medicine’, detailed insight into the underlying mechanisms is warranted. In murine cancer models immune cell mobilisation leads to control of tumour growth through increased infiltration by immune cells in the tumour tissue in a manner dependent on release of adrenalin and IL-6. To look further into these mechanisms in humans, we studied the NK cell mobilisation -and characteristics in healthy subjects or cancer patients undergoing neo-adjuvant chemotherapy participating in an acute bout of exercise.Material and methodsBlood immune cell profiles were evaluated in 5 healthy subjects performing either 2 hours of interval-based cycling or 2 hours of cycling at constant Watt intensity, and in 4 patients with cancer of the gastro-esophageal junction (GEJ) performing an acute bout of interval-biking followed by resistance training. Blood was collected before training, after warm-up, during training, and after a resting period. The samples were analysed by flow cytometry staining for CD3, CD19, CD14, CD16, CD56, and HLA-DR for differentiation of T cells, B cells, NK cells, and monocytes. The abundance of Granzyme B and Ki67 reflected cytotoxic profile and proliferation status, respectively.Results and discussionsIn healthy subjects, we observed a rapid up to 4-fold mobilisation of NK cells to the circulation, as well as increased Granzyme B content, decreased Ki-67 expression, and increased cellular size in the mobilised NK cells. These findings were particularly evident with interval-based training. In the 4 GEJ cancer patients we found up to 8-fold increase in circulating NK-cells after 35 min of interval-based cycling, along with increases in Granzyme B abundance and decreased Ki67 expression.ConclusionAn acute bout of interval-based exercise mediates recruitment of cytotoxic NK cells to the circulation in both healthy young men and GEJ cancer patients undergoing neo-adjuvant chemotherapy. Furthermore, immune cell mobilisation in the cancer patients was comparable to (if not better than) the recruitment observed in healthy subjects.