CD274 and melanoma: In summary, this work presents evidence supporting the anti-tumor function of exercise, offers a detailed explanation of how exercise improves the tumor microenvironment and enhances the immune response against tumors by alleviating hypoxia and demonstrates the effectiveness and safety of exercise-enhanced PD-1/PD-L1 blockade, which shedding light on the positive role of exercise in tumor therapy and presenting a potential avenue for enhancing melanoma immunotherapy.