Can Exercise-Induced Modulation of the Tumor Physiologic Microenvironment Improve Antitumor Immunity?

Both obesity and sedentariness have been linked to increased risk for a wide range of cancers. While there is some evidence that weight loss (e.g. through bariatric surgery) can reduce the incidence of and deaths from malignancies, the role of exercise on cancer morbidity and mortality is less clear. Although a growing body of literature suggests that increased physical activity can reduce the mental and physical stress of living with cancer, its role in directly influencing the malignant process is less clear.

Now, a paper by Xiaojie Zhang and colleagues, published in Cancer Research, discusses the many ways in which exercise may potentially promote the body’s ability to fight cancer by modulating the tumor microenviroment.

As the authors point out, “Preclinical and human studies suggest that exercise elicits mobilization of leukocytes into circulation (also known as “exercise-induced leukocytosis”), especially cytotoxic T cells and natural killer cells. However, the tumor physiologic microenvironment presents a significant barrier for these cells to enter the tumor and, once there, properly function.

Among the mechanisms by which exercise can alter immunological response to tumors, the authors include positive changes to the tumor microvasculature as well as the tumor microenviroment including decreased hypoxia, hypoglucosis, lactosis, and reduced pH. For each of these potential mechanisms (that are likely to work in concert), the authors discuss current evidence from animal models that would support these potentially beneficial effects of exercise.

While we have yet to see a definitive controlled study on the long-tem benefits of exercise treatments on cancer survival (and not just rehabilitation and well-being), the authors make a strong case that such studies are perhaps long overdue. In addition, “Rigorous studies that elucidate the link between exercise and immune cell function in the tumor microenvironment and in the periphery will also serve as a guide of how to implement exercise in the context of immunotherapies that harness the immune system against cancer.

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