Lung cancer is our most fatal malignancy, accounting for 28% of all cancer-related deaths. In fact, more people die from lung cancer than breast, colon and prostate cancer combined. Approximately two thirds of patients with non-small cell lung cancer (NSCLC – accounts for 85% of all lung cancers) will present with surgically unresectable disease and those with “curable” disease frequently go on to develop loco-regional and/or distant metastasis, the result of which ultimately leads to death. Immunotherapy has shown great promise with improved outcomes and prolonged survival in a wide variety of cancers, including NSCLC. However, there is room for improvement as objective response rates are ~20-50%, depending on patient selection criteria and therapeutic combinations. Currently, approximately 60% of all NSCLC patients treated with immunotherapy will fail to respond and an even larger proportion will fail to respond to systemic chemotherapy. The need for improved systemic therapies for this disease is unmistakable and our lab uses both computational and traditional wet lab approaches to identify and validate novel regulators of cancer progression.