Research Project: Inhibiting CD24 May Improve Immune-Based Treatment for Lung Adenocarcinoma
Lung Cancer Discovery Award
basic biologic mechanisms
Lung adenocarcinoma (LUAD) is the most common type of lung cancer and the leading cause of cancer deaths among smokers. It is increasingly being detected in early stages largely due to enhanced screening. Improved treatment of this growing cancer population heavily relies on understanding changes that underlie its development and escape from immune system surveillance. Recently we probed genetic and immune changes in each individual cell from early-stage LUADs. We found that the cell surface molecule CD24 is greatly expressed on cancerous cells and in the earliest precursors of LUAD, promotes tumor growth, and is associated with poor response to immune-based therapy. We will first understand the role of CD24 in early LUAD development and then determine the effects of inhibiting this promising target on immune-based treatment of cancer. The findings will lay the groundwork for clinical trials to develop new strategies for early immune-based treatment of LUAD.
This year we made progress in understanding the role of a potential lung tumor cell-specific immune checkpoint (CD24) in the development and growth of lung adenocarcinoma. We were able to perform a number of experiments to study the role of CD24 in lung cancer growth, immune microenvironment and in response to established immune checkpoint inhibitors (anti-PD-1 antibodies). We have started experiments using novel mouse models for lineage-specific deletion of CD24.