Investigating the Role of Nitric Oxide in the Immune Regulation of Non-Small Cell Lung Cancer
Abstract
A main contributor to respiratory diseases is the constant exposure to air pollutants during the deployment of military personnel. During operations, military personnel are exposed to multiple factors external to the conflict, including air contaminants and pollutants that affected their health. Most military personnel have reported acute respiratory effects due to exposure to air contaminants. The main sources of air pollutants are diesel exhaust, sandstorms, firearms fumes and smoke from burn pits. Studies have shown these pollutants highly contribute to lung pathologies among military personnel, increasing the prevalence of lung inflammatory diseases. Burn pit smoke is considered the major source of air pollution in the field. Studies have shown the correlation between exposure to burn pit smoke and cancer development. Inhalation of combustion fumes alters the expression of different metabolic enzymes, including nitric oxide synthases (NOS1, NOS2, NOS3). In healthy tissues, NOS isoforms modulate an array of cell transduction signals that control tissue vascularization, immune regulations and tissue repair. Deregulation of the balance of expression of the different isoforms increases the production of nitric oxide in cells, altering nitration and nitrosylation of proteins. These post-translational modifications of proteins have been associated with lung inflammatory disease and alteration of the immune response. Specifically, overexpression of NOS2 and NOS3 is associated with worst prognosis in lung adenocarcinoma. Our proposal addresses the role of the different NOS isoforms in regulating the visibility of tumor cells to the immune system and how they participate in the remodeling of the tumor microenvironment, addressing an issue of huge importance to military personnel exposed to combustion fumes. In our analysis of lung adenocarcinoma, we have found that the type of immune infiltration (myeloid or lymphoid) was predictive of patient outcome.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2024
- Accession Number
- AD1230174
Entities
People
- Anthony Purcell
- Marie-liesse Asselin-labat
Organizations
- Monash University
- WEHI