Physical Exercise in Immunotherapy

Accumulating evidence suggests that physical exercise can favorably modulate the tumor microenvironment (TME) and enhance the efficacy of cancer immunotherapies. MAIN: Exercise has been shown to modulate the immune environment to promote infiltration and function of cell types that confer anti-tumor effects. These effects counteract several mechanisms of immune evasion within the TME that limit the effectiveness of immune checkpoint blockade, particularly therapies targeting PD-1 and PD-L1. Preclinical models demonstrate that exercise not only enhances anti-tumor immune responses, but also sensitizes tumors to checkpoint inhibitors, resulting in improved tumor control. Mechanistically, these benefits appear to be mediated through enhanced cytokine signaling, metabolic reprogramming of immune cells, and alterations in chemokine gradients that facilitate immune cell trafficking.

This review summarizes current insights into how exercise impacts tumor biology and immunity and discusses the emerging rationale for integrating structured physical activity into immunotherapeutic regimens. While clinical evidence remains limited, ongoing studies will be critical to determining the translational relevance of these findings across cancer types and patient populations.