Regulatory T Cells May Link Obesity and Lung Cancer

In an interview with Targeted Onc™, Sai Yendamuri, MD, MBA, FACS, discusses research investigating the relationship between obesity and lung cancer development, including the potential role of regulatory T cells in mediating obesity-associated carcinogenesis. The study was prompted by findings from lung cancer risk prediction models suggesting that higher body mass index (BMI) was associated with a lower risk of lung cancer, despite evidence linking obesity to chronic inflammation and cancer development.

To better characterize this relationship, investigators used computed tomography (CT) imaging to assess total body fat in individuals at high risk for lung cancer and those with early-stage disease. Patients with early-stage lung cancer had a greater proportion of body fat than those who were at high risk but had not developed cancer.

The team then used mouse models to investigate potential mechanisms, finding that obese mice developed cancer more frequently following carcinogen exposure than lean mice. Further analysis identified increased regulatory T-cell activity as a potential contributor to obesity-associated tumor development.

To determine whether these findings translated to humans, investigators evaluated immune cell populations in bronchial lavage samples from patients undergoing bronchoscopy. Consistent with the preclinical findings, patients with higher levels of body fat demonstrated greater regulatory T-cell activity.

Yendamuri describes the investigation as a bedside-to-bench-and-back-to-bedside approach, integrating clinical observations, preclinical modeling, and human immune profiling. The findings provide a potential biological explanation for the relationship between obesity and lung cancer incidence and support further investigation of obesity-targeting strategies as a possible approach to lung cancer prevention.