Obesity weakens anti-tumor immune response in lung cancer, but exercise may restore it

by Roswell Park Comprehensive Cancer Center

edited by Lisa Lock, reviewed by Andrew Zinin

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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 this effect.

"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. Yendamuri and Andrew Ray, PT, Ph.D., associate professor of oncology in the Department of Cancer Prevention & Control, are senior authors of the study, which is published in the Annals of Surgery.

Using RNA sequencing and flow cytometry, the research team compared the effects of exercise on tumors and infiltrating leukocytes—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 nonexercising 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 antitumor response, and more CD8⁺ T cells, which can actively destroy tumors. 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, noninvasive adjunct to a patient's treatment regimen that has the potential to improve outcomes," Ray says.

Publication details

Randall Smith et al, Exercise Modulates Adiposity-induced Immune Dysfunction in NSCLC and Non-tumor–Bearing Lungs: Implications for Lung Cancer Therapy and Interception, Annals of Surgery (2026). DOI: 10.1097/sla.0000000000007151

Journal information: Annals of Surgery

Key medical concepts

ObesityCarcinoma, Non-Small-Cell LungT-Lymphocytes, Regulatorytumor growth

Clinical categories

OncologyFitness & Physical activityAllergy and immunologyWeight management Provided by Roswell Park Comprehensive Cancer Center Who's behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

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