Pulmonary innervation, inflammation and carcinogenesis

Lung cancer is a major medical problem. Despite advances in molecular biology and pharmacology, the outcome of lung cancer treatment is unsatisfactory. Clinically, inflammation and cancer are closely associated, and, genetically, these two processes are regulated by the same gene loci. Inflammation promotes cancer formation. Increasing evidence shows that neuroimmune interaction involving inflammatory disease and the vagus nerves are crucial in the interaction. Airway sensory receptors are biosensors that detect the lung inflammatory process through various mediators and cytokines. This information is transmitted through vagal afferents to the brain and produces a host of responses that regulate the extent and intensity of inflammation. Tumor cells express receptors for neurotransmitters and provide a substrate for direct interaction with neurons. Thus, neural regulation of the immune response is targeted towards inflammation as well as tumors. The airway sensors can detect cancer-related cytokines, which provides a direct pathway to inform the brain of tumor growth. The knowledge of how these sensors may monitor tumor progression and provide neuroimmune interaction in the control of tumor development and metastasis will improve our treatment of lung cancer.