Lung cancer is the leading cause of cancer death for both men and women worldwide with an estimated 1,796,00 deaths associated with the disease in 2020. The high mortality rate is due to the poor early detection of tumours as symptoms of NSCLC generally only appear at latter stages of the disease. Therefore, it is imperative to have a better understanding of the initiating events leading to tumour development.

Previous studies using mice have shown that influenza infection leads to an expansion of airway epithelial stem cells throughout the distal parts of the lung. This process is regarded as aberrant and leads to bronchiolisation of the alveolar epithelium leading to inflammation and fibrosis. Given that cancer and regeneration are closely linked we hypothesised that an induced influenza injury in the lung combined with epithelial stem cells harbouring mutations would lead to the acceleration of NSCLC tumour development.

To show this, we used a previously described transgenic LKB1Fl/Fl PTENFl/Fl mouse model which was shown to produce NSCLC tumours 40-50 weeks post the induction of adenovirus containing cre-recombianse (adeno-cre). Using this model, we added infection with a mouse adapted h3n2 strain of influenza (Hx31) 14 days post adeno-cre inoculation to initiate widespread remodelling.

We discovered that mice treated with Hx31 post adeno-cre inoculation developed tumours significantly faster than the adeno-cre, saline group. We also observed a significant increase in hyperplastic and dysplastic airways at earlier timepoints in the adeno-cre, Hx31 group.

These results indicate that pathogenic infection in the context of mutatated epithelial stem cells can accelerate tumour formation.