Project Title: Predictors of disease relapse in early-stage non-small cell lung cancer (ES-NSCLC)

Aim/goals:

1. Identify the composition of ES-NSCLC cells and the tumour microenvironment (TME) in the background of lung injury as measured by the total mutation burden and gene expression.
2. Determine the TME associated with ES-NSCLC with a special focus on the immune cell compartment.
3. Measure tumour and adjacent tissue properties that correlate with metastatic relapse.

Lung cancer is the leading cause of cancer related death in men and women in Canada. Non-small cell lung cancer (NSCLC) accounts for 88% of cases. Early-stage NSCLC (ES-NSCLC) is potentially curable with aggressive local therapies like surgery or ablative radiation. However, even Stage I and II disease have 3-year survival below 30%, due to metastatic disease relapse. The imminent adoption of CT-based lung cancer screening across Canada means more patients will be diagnosed with ES-NSCLC. Understanding the tumor microenvironment (TME) of ES-NSCLC may help optimize patient treatment and improve survival.

Tissue injury and inflammation contributes to tumorigenesis by disrupting the usual balance in the adaptive immune response. Lung injury including from tobacco smoke, chronic lung disease, and environmental factors contributes to inflammation and mutagenic effects that promote a cancer-favouring immune response. Immune-checkpoint modifiers that alter T-cell function predominantly through the PD1/PD-L1 axis have demonstrated improved survival in randomized control trials for patients with early and advanced disease stage.

Our multi-disciplinary research team is keen on understanding biomarkers associated with disease prognosis with an emphasis on the role of inflammation and tissue injury on lung cancer initiation and dissemination. We hypothesize that TME influenced by exposure- and treatment related- lung injury interact with tumor cells and contributes to invasion and distant metastases.

Our cohort consists of Stage I/II NSCLC treated for cure with surgery. We will select ES-NSCLC cases with disease relapse within 5 years of surgery matched 1:1 with cases that remain disease free during this same period. Genomic profiling through the MOHCCN will help explore if biological changes can be identified between these cases with different disease trajectories.