The tumor immunotherapy sensitizing with the correction of hypoxia in tumor microenvironment by the exercise treatment

Although the emerging immunotherapy revolutionized the cancer treatment, significant challenges remain to be addressed with regard to the limited efficacy, the insufficient anti-tumor spectrum and some immune-related adverse events. To overcome these obstacles, considerable progress has been achieved in rectifying the anoxic tumor microenvironment (TME) to restore the potency of immunotherapy from the hypoxic immunosuppression. The exercise treatment is a class of health, non-traumatic and low-side-effect adjuvant therapies, which can modulate immunity. Therefore, to verify the hypothesis that the exercise treatment can sensitize the tumor immunotherapy, we established an allograft B16F10 melanoma model based on C57/B6 mice with the completely immune. As expected, both low-intensity exercise and moderate intensity exercise can rectify the hypoxia in TME and enhanced the infiltration and the subsequent tumor lethality, resulting in the sensitization of tumor immunotherapy by the PD1 neutralizing antibody, with favorable safety and efficacy. Collectively, the present work verifies the mechanism of action of exercise on tumor immunotherapy, but also provides feasible ideas for novel anti-tumor sensitized immunotherapy.