Obesity Promotes Lung Carcinogenesis Through Airway Immune Dysfunction

Gene expression in high-TFA airways suggested suppressed immune activity. Compared to lean controls, the lungs of obese mice displayed abundant potentially suppressive myeloid cells, activated Regulatory T cells, and effector T cell deficits at baseline and during carcinogenesis, which was significantly exacerbated by obesity. Functional assays and depletion studies suggested obesity-enhanced Tregs can potentiate rapid tumor growth, and flow analysis of patients airway leukocytes further suggest compromised lung immune surveillance in patients of high TFA.

Conclusions: Obesity is associated with enhanced lung carcinogenesis. Mechanisms of immune suppression upregulated with excess adiposity, including activated, functional Tregs, are evident in clinical and preclinical systems. These results refute the concept of an obesity paradox for lung cancer risk.