Leveraging the Immunoproteasome to enhance Immunotherapy in non-small cell lung cancer

Lung cancer is the second most common cancer in both men and woman, and non-small cell lung cancer accounts for 80% of lung cancer cases. Across cancer types, therapies that enhance immune responses to cancers have made a huge impact on improving outcomes for patients. Presentation of antigen is necessary for immune recognition of tumor cells and hence for activity of almost all forms of immunotherapy including immune checkpoint inhibition (ICI), vaccination, CAR-T cell or T-cell engager therapies. The immunoproteasome is a specialised form of the proteasome endowed with differentiated attributes that allow maintenance of proteastasis and superior generation of antigenic peptides. We have projects involved in three aspects of the immunoproteasome 1. Genomic validation (ie bioinformatics and genetic studies) of the immunuproteasome. 2. Mechanistic screens of immunoproteasome function by CRISPR forward genetics 3. Drug screens to identify small molecules that enhance immunoproteasome function. This goal of this project is to develop novel immunoproteasome-targeting strategies for cancer immunotherapy.