Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths in the US, despite the fact that some patients benefit from checkpoint blockade therapy.
Anti-PD1/PD-L1 checkpoint blockade therapy is effective in a fraction of patients with NSCLC, and when effective often mediates durable responses. Understanding the differences between immunotherapy-sensitive, T cell-inflamed and immunotherapy-insensitive, non-T cell-inflamed tumors on a molecular level will facilitate the development of novel treatment combinations for this disease. Previous studies have provided evidence that tumor cell-intrinsic activation of signaling pathways (e.g. WNT/beta-catenin) mediates exclusion of T cells from the tumor microenvironment. We aim to compare and study T cell-inflamed and non-T cell-inflamed lung adeno and lung squamous carcinomas in order to identify tumor cell-intrinsic signaling alterations affecting the local anti-tumor immune response. By generating new genetically-engineered mouse models for lung cancer we plan to elucidate dominant tumor cell-intrinsic signaling pathways impairing productive anti-tumor immune responses.
Schematic illustrating T cell-inflamed (red) and non-T cell-inflamed (blue) lung cancer.