Humam Kadara, PhD

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.

Update:
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.

Final Project Update: 
We have focused on CD24, a cell surface protein that has been implicated in tumor growth, invasion and metastasis. Our findings suggest that CD24 is elevated in the earliest phases of lung adenocarcinoma (LUAD), a type of non-small cell lung cancer (NSCLC) that is the most common type of lung cancer. We found that CD24 may also be modulated in immune cells called B cells during LUAD development. Our findings suggest that increased CD24 is likely associated with reduced response in people with early stage disease to treatment with a combination of neoadjuvant CT and immune checkpoint inhibitor (ICI) therapy, which is given before surgery to shrink tumors or stop the spread of disease. These findings suggest that CD24 could be therapeutically leveraged in combination with ICIs for early immune-based treatment of LUAD. Our findings also suggest that CD24 is a viable target to also enhance response to approved and emerging therapies that target the KRAS mutation in lung cancer. 

Supported by the Mary Fuller Russell Fund