Exercise and the immune system: taking steps to improve responses to cancer immunotherapy

Abstract

The remarkable success of cancer immunotherapies has provided new hope to cancer patients. Unfortunately, a significant proportion of patients remain unable to respond to immunotherapy or maintain durable clinical responses. The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients. As the immune system is highly responsive to exercise, one potential avenue to improve immune function is through exercise and physical activity. A single event of dynamic exercise results in the substantial mobilization of leukocytes with increased functional capacities into the circulation. Chronic, or long-term, exercise leads to higher physical fitness in terms of greater cardiorespiratory function and/or muscle strength and endurance. High aerobic capacity, as measured by maximal oxygen uptake, has been associated with the reduction of dysfunctional T cells and improvements in the abundance of some T cell populations. To be sure, however, the mechanisms of exercise-mediated immune changes are both extensive and diverse. Here, we examine the evidence and theorize how acute and chronic exercise could be used to improve responses to cancer immunotherapies including immune checkpoint inhibitors, dendritic cell vaccines, natural killer cell therapies, and adoptive T cell therapies such as chimeric antigen receptor (CAR) T cells. Although the parameters of optimal exercise to yield defined outcomes remain to be determined, the available current data provide a compelling justification for additional human studies and clinical trials investigating the adjuvant use of exercise in immuno-oncology.

The Effects of Physical Activity on Cancer Patients Undergoing Treatment with Immune Checkpoint Inhibitors: A Scoping Review

“…There is a growing body of evidence investigating the mechanisms by which exercise modulates immunity. Much of this research points to effects on natural killer (NK) and T cells, rather than to components of humoral immune responses [ 7 ]. These are also the immune cells that are targeted by ICIs, indicating that the anti-tumor effects of both exercise and checkpoint blockade may be synergistic.…”

“…Physical activity has been previously shown to be effective in the milieu of chemotherapy for decreasing the severity of chemotherapy- and cancer-related side effects [ 3 , 4 , 5 ]. Similarly, physical activity has been shown to reduce CRF and modulate the immune system through multiple mechanisms in cancer patients [ 6 , 7 ].…”

Circadian rhythms and cancers: the intrinsic links and therapeutic potentials

“…Exercise can modulate the circulation of immune cells by a mechanism mediated by adrenergic signaling and blood flow-induced shear stress, facilitating immune surveillance by eradicating identified malignant cells [ 179 ]. Indeed, an increasing number of studies have found exercise-induced immune cell mobilization as a common phenomenon independent of age, gender, or tumor type [ 180 , 181 ].…”

The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients

“…Chronically, physical activity promotes executive function, increases neurogenesis of the hippocampus and reduces inflammation as well as promotes healthy function of many of the organ systems of allostatic responses. Together, the effects of physical activity can be expected to reduce acute activation, promote habituation to future stressors and counteract adverse effects of allostatic load on target organ systems [ 145 , 146 ].…”