Obesity Weakens Anti-Tumor Immune Response in Lung Cancer – But Exercise May Restore It

Obesity can weaken the immune system’s tumor-killing responses in lung cancer, leading to disease progression, but a new study by experts at Roswell Park Comprehensive Cancer Center reveals that exercise may reverse that effect. Sai Yendamuri, MD, MBA, FACS, Chair, Department of Thoracic Surgery, and Andrew Ray, PT, PhD, Associate Professor of Oncology, Department of Cancer Prevention & Control, are senior authors of the study, which appears in Annals of Surgery.

“This study demonstrates how exercise can correct immune dysfunction in the lungs to provide a stronger defense against tumors,” says Dr. Yendamuri.

Using RNA sequencing and flow cytometry, the research team compared the effects of exercise on tumors and infiltrating leucocytes — white blood cells that can destroy tumor cells — in four groups of mice: obese or lean healthy mice that either had access to an exercise wheel or were sedentary, and obese or lean mice with non-small cell lung cancer (NSCLC) that could exercise or were sedentary. Compared with non-exercising lean mice that were either healthy or had lung cancer, obese mice with or without lung cancer that were physically active had fewer regulatory T cells (Tregs), which suppress the anti-tumor response, and more CD8+ T cells, which can actively destroy tumors, and tumors grew more slowly in the exercising NSCLC mice.

Researchers also analyzed cell samples from the lungs of 73 patients with non-small cell lung cancer who were categorized according to total fat area and level of physical activity. Samples from those who exercised contained both fewer Tregs and fewer fat-enhanced myeloid cells, which can suppress the body’s tumor-killing response.

“Exercising can provide a free, non-invasive adjunct to a patient’s treatment regimen that has the potential to improve outcomes,” says Dr. Ray.

The work was supported by National Cancer Institute / National Institutes of Health grant R01CA222382 to Dr. Ray and grant R01 CA255515-01A1 to Dr. Yendamuri and Joseph Barbi, PhD.