Regular physical activity may counteract obesity-induced immune suppression in the lungs, potentially restoring the body’s natural defenses against non-small cell lung cancer, according to a peer-reviewed study published August 6, 2026, in the Annals of Surgery. Researchers found that voluntary exercise reduced the accumulation of tumor-promoting immune cells and preserved cytotoxic T-cell activity in obese subjects, offering a new biological mechanism for how lifestyle interventions might complement cancer immunotherapy.
How Obesity Drives Lung Immune Dysfunction and Tumor Growth
Obesity creates a systemic inflammatory and metabolic state that fundamentally alters immune cell function, paving the way for tumor progression. In lung cancer, excess adipose tissue drives the expansion of immunosuppressive populations—such as regulatory T cells (Tregs)—while simultaneously suppressing the activity of CD8+ cytotoxic T cells responsible for destroying malignant cells. According to Roswell Park Comprehensive Cancer Center researchers, these detrimental alterations extend directly into the pulmonary compartment and tumor microenvironment, weakening the body’s natural tumor-killing response.
Experimental Findings in Active Obese Models
To evaluate whether physical activity could reverse these deficits, investigators at Roswell Park analyzed four distinct groups of mice, comparing lean and obese subjects with and without Lewis lung carcinomas under sedentary conditions or with access to exercise wheels. Using RNA sequencing and flow cytometry, the research team discovered that obese mice with voluntary exercise access displayed fewer Tregs and suppressive myeloid cells, alongside fewer CD8+ T-cell deficits in both the tumor and the lung tissue. Active obese mice also experienced significant delays in tumor growth, whereas lean mice experienced comparatively muted physiological effects from the same activity level.
Evidence From Human Pulmonary Samples
To determine if these animal models translated to human physiology, the study examined bronchoalveolar lavage samples from 73 patients diagnosed with non-small cell lung cancer. Investigators stratified these human samples according to total fat area and self-reported physical activity, applying multivariable adjustments to the data. The analysis revealed that physically active patients exhibited notable reductions in PD-1+ Tregs and fat-enhanced suppressive myeloid cells compared to their sedentary peers.
“This study demonstrates how exercise can correct immune dysfunction in the lungs to provide a stronger defense against tumors,” says Sai Yendamuri, MD, MBA, FACS, chair of the Department of Thoracic Surgery at Roswell Park and senior study author. Andrew Ray, PT, PhD, associate professor of oncology in the Department of Cancer Prevention and Control and co-senior author, adds that physical activity represents a non-invasive adjunct to standard care. “Exercising can provide a free, non-invasive adjunct to a patient’s treatment regimen that has the potential to improve outcomes,” says Dr. Ray.
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