Exercise-Induced Engagement of the IL-15/IL15Rα axis Promotes Anti-Tumor Immunity

Abstract Tumor-infiltrating immune cells play a central role in controlling cancer development and progression, as well as in responses to therapeutic interventions. However, the mechanisms that control their mobilization, composition, and function are not completely understood. Here, we show that aerobic exercise is sufficient to induce an intra-tumoral expansion of activated CD8 T cells and a reduction in tumor growth in murine models of pancreatic cancer. Specifically, exercise-induced spikes in epinephrine promote a systemic immune mobilization and accumulation of tumor-infiltrating IL15Rα+ CD8 T cells. This sub-population of activated CD8 T cells is responsible for the tumor protective and immune activating benefits of aerobic exercise, as both are abrogated in the context of IL-15 antagonism. Notably, the anti-tumor effect of aerobic exercise is potentiated by PD-1 blockade, suggesting a therapeutically exploitable link between an exercise-oncology axis and immune intervention strategies in a largely intractable disease.