title: COPD and squamous cell lung cancer: aberrant inflammation and immunity is the common link.
abstract: Cigarette smoking has reached epidemic proportions within many regions of the world and remains the highest risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Squamous cell lung cancer is commonly detected in heavy smokers, where the risk of developing lung cancer is not solely defined by tobacco consumption. Although therapies that target common driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related squamous cell lung cancer. Since COPD is characterized by an excessive inflammatory and oxidative stress response, this review details how aberrant innate, adaptive and systemic inflammatory processes can contribute to lung cancer susceptibility in COPD. Activated leukocytes release increasing levels of proteases and free radicals as COPD progresses and tertiary lymphoid aggregates accumulate with increasing severity. Reactive oxygen species promote formation of reactive carbonyls that are not only tumourigenic through initiating DNA damage, but can directly alter the function of regulatory proteins involved in host immunity and tumour suppressor functions. Systemic inflammation is also markedly increased during infective exacerbations in COPD and the interplay between tumour-promoting serum amyloid A (SAA) and IL-17A is discussed. SAA is also an endogenous allosteric modifier of FPR2 expressed on immune and epithelial cells, and the therapeutic potential of targeting this receptor is proposed as a novel strategy for COPD-lung cancer overlap.
authors.affiliation: School of Health Sciences and Health Innovations Research Institute, RMIT University, Melbourne, Vic., Australia.|Lung Health Research Centre, Department of Pharmacology & Therapeutics, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Bozinovski
authors.affiliation: School of Health Sciences and Health Innovations Research Institute, RMIT University, Melbourne, Vic., Australia.|Lung Health Research Centre, Department of Pharmacology & Therapeutics, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Vlahos
authors.affiliation: Lung Health Research Centre, Department of Pharmacology & Therapeutics, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Desiree
authors.initials: D
authors.lastname: Anthony
authors.affiliation: Lung Health Research Centre, Department of Pharmacology & Therapeutics, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McQualter
authors.affiliation: Lung Health Research Centre, Department of Pharmacology & Therapeutics, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Gary
authors.initials: G
authors.lastname: Anderson
authors.affiliation: Department of Respiratory Medicine, The Royal Melbourne Hospital, Parkville, Vic., Australia.
authors.forename: Louis
authors.initials: L
authors.lastname: Irving
authors.affiliation: Department of Respiratory Medicine, The Royal Melbourne Hospital, Parkville, Vic., Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Steinfort
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000503:physiopathology*