(Denver, Colo — October 8, 2026) – In a recent study of more than a thousand individuals, greater adiposity, or excessive body fat or fatty tissue, specifically in the abdomen, was associated with lung cancer. These findings and complementary laboratory studies published in the Journal of Thoracic Oncology suggest obesity may create an immunosuppressive environment in the lungs that allows emerging cancer cells to escape immune surveillance.
JTO is the official journal of the International Association for the Study of Lung Cancer. The full study is available here: https://www.jto.org/article/S1556-0864(26)00519-8/fulltext.
Researchers led by Joseph Barbi, PhD, and Sai Yendamuri, MD, MBA, FACS, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., analyzed CT scans and clinical information from 1,170 high-risk individuals, including 594 patients with early-stage lung cancer and 576 individuals without lung cancer. Patients with lung cancer had significantly greater total abdominal fat area than controls, while body mass index (BMI) did not differ significantly between the two groups.
The findings challenge what researchers have called the “obesity paradox” in lung cancer—a notion that stemming from previous studies that used BMI to identify obese and overweight patients that have sometimes suggested an inverse relationship between adiposity and lung cancer risk. However, BMI is increasingly regarded as an imperfect measure of adiposity because it does not speak directly to body composition or fat distribution.
In the current study, the investigators used total abdominal fat area (TFA) measured from CT scans rather than relying exclusively on BMI. Their analysis found a median TFA was 300.7 cm² among patients with lung cancer compared with 267 cm² among controls (p=0.006). By contrast, median BMI was 26.9 kg/m² in the lung cancer group and 26.4 kg/m² among controls, a difference that was not statistically significant.
After accounting for factors including age, sex and smoking status, TFA remained significantly associated with the presence of lung cancer. Among participants with higher BMI, individuals with lung cancer also had significantly greater abdominal fat than individuals in the screening cohort.
The researchers then looked beyond the epidemiologic association to investigate a possible biological explanation. Analysis of airway gene-expression data from additional patients suggested that greater adiposity was associated with suppression of immune pathways that normally help the body identify and eliminate malignant cells.
To explore that mechanism more directly, investigators compared normal-weight mice with those made obese on a high-fat diet. The obese mice exhibited significant changes in the immune environment of their lungs, including increased populations of regulatory T cells and potentially suppressive myeloid cells, along with evidence of impaired effector T cell activity.
Using both genetically driven and chemically induced models of lung carcinogenesis, researchers also found that obesity significantly increased lung tumor development. The experiments allowed investigators to examine changes in immune-cell populations as cancer developed and provided evidence that obesity may impair the lung’s ability to eliminate newly emerging malignant cells.
Additional experiments strengthened that potential mechanistic connection. Regulatory T cells isolated from the lungs of obese mice were significantly more effective at suppressing the proliferation of responder T cells than those obtained from normal-weight animals. Cellular analysis of the bronchoalveolar lavage samples from 109 patients confirmed that several of the obesity-associated changes seen in mice are relevant to the human airway in the setting of high adiposity.
These findings suggest that excess adiposity may alter the immune environment of the airway in ways that favor the initiation and persistence of lung tumors – and offer a potential explanation for adiposity-associated lung cancer risk.
The researchers said the findings help reconcile the apparent contradiction between previous BMI-based epidemiologic studies and extensive evidence that obesity can impair antitumor immunity.
“Overall, our data clearly associate central adiposity with heightened lung cancer risk,” Dr. Barbi writes, adding that the findings strongly implicate increased immune-suppressing mechanisms in the airways of obese mice and patients as a potential contributing factor.
The authors conclude that obesity is associated with enhanced lung carcinogenesis and that immune-suppressive mechanisms associated with excess adiposity—including activated regulatory T cells—are evident in both clinical and preclinical systems. The results, they said, not only challenge the concept of an obesity paradox with respect to lung cancer risk but, importantly, they also call attention to specific obesity-associated changes in the airway immune system. Ongoing efforts aimed at reversing these effects with current or novel therapies may provide the means to combat lung cancer development in those who are overweight or obese – populations that continue to grow in much of the world.
About the IASLC
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 11,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the JTO
Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer, is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. JTO emphasizes a multidisciplinary approach and includes original research reviews and opinion pieces. The audience includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.
Journal of Thoracic Oncology
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