Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity?

Abstract

Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor microenvironment. Exercise is known to promote immune cell circulation and improve immunosurveillance. Results of recent studies indicate that physical activity can induce mobilization and redistribution of immune cells towards the tumor microenvironment (TME) and therefore enhance anti-tumor immunity. This suggests a favorable impact of exercise on the efficacy of ICI. Our review delivers insight into possible molecular mechanisms of the crosstalk between muscle, tumor, and immune cells. It summarizes current data on exercise-induced effects on anti-tumor immunity and ICI in mice and men. We consider preclinical and clinical study design challenges and discuss the role of cancer type, exercise frequency, intensity, time, and type (FITT) and immune sensitivity as critical factors for exercise-induced impact on cancer immunosurveillance.

Combined effects of exercise and immuno-chemotherapy treatments on tumor growth in MC38 colorectal cancer-bearing mice

“…Furthermore, only a few rodent studies combined exercise with immuno-chemotherapy in various clinical cancer settings. Several murine studies have investigated the combination of immunotherapy with exercise in different types of cancer including breast cancer, melanoma liver and lung carcinoma with divergent results ( 23 , 24 ). Overall, the tumor models (i.e.…”

Crosstalk between Exercise and Immunotherapy: Current Understanding and Future Directions

“…Currently, the majority of research on exercise and its impact on immunotherapy efficacy are conducted on animal models, with limited clinical data available. Existing randomized controlled trials primarily focus on the physiological and psychological effects of exercise on cancer patients receiving immunotherapy [ 15 – 17 ], as well as the changes regarding immune and inflammatory biomarkers in blood samples [ 18 , 19 ]. However, overall survival, PFS, and ORR are supposed to be considered to assess the long-term influence of immunotherapy in combination with exercise training on cancer patients [ 20 ].…”

Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases

“…The effects of physical exercise on cancer growth and treatment efficacy are generally positive [133,134]. Physical exercise was shown to enhance anti-PD-1 immunotherapies [135,136] and the efficacy of checkpoint inhibitors [137], and reduce doxorubicin-mediated cardiotoxicity in mice [138]. Stretching exercises for 10 min every day for 4 weeks in breast cancer mice models significantly reduced tumor volume and growth, as compared to the control group [139].…”