Student and Faculty Publications
Publication Date
5-20-2023
Journal
Frontiers in Immunology
Abstract
INTRODUCTION: Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable
METHODS: In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on K-ras-driven lung adenocarcinoma.
RESULTS: We found that knockout of TLR 2, 4, or 9 results in a lower tumor burden, reduced angiogenesis, and tumor cell proliferation, accompanied by increased tumor cell apoptosis and reprogramming of the tumor microenvironment to one that is antitumorigenic. Additionally, knocking out of downstream signaling pathways, MyD88/NF-κB in the airway epithelial cells further recapitulated this initial finding.
DISCUSSION: Our study expands the current knowledge of the roles that TLR signaling plays in lung cancer, which we hope, can pave the way for more reliable and efficacious prevention and treatment modalities for lung cancer.
Keywords
Mice, Animals, NF-kappa B, Toll-Like Receptor 2, Myeloid Differentiation Factor 88, Lung Neoplasms, Inflammation, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, Epithelium, Pulmonary Disease, Chronic Obstructive, Tumor Microenvironment, COPD, KRAS, toll-like receptor, lung cancer, IKK beta, MyD88
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons, Pulmonology Commons, Respiratory Tract Diseases Commons
Comments
Supplementary Materials
PMID: 37283745