Veterans Medical Research Foundation
Disrupting Complex Sugars on Immune Cells Could Inhibit Growth of Lung Cancer
We will identify how disrupting a unique complex sugar molecule known as heparan sulfate (HS) on immune cells called dendritic immune cells (DCs) may inhibit cancer growth. DCs in lung cancer often become poorly functional and immature, ultimately promoting suppression of the immune system by inhibiting the actions of anti-tumor immune cells called T cells. We will study the mechanisms that govern the movement and maturation of dendritic immune cells that are dependent on HS, examining how the targeted molecular changes affect their movement and ability to interact with T cells. Using mouse models of lung cancer, we will also begin to examine how novel HS inhibitors might boost the ability of dendritic cells to fight cancer. This research could lead to new strategies to cure cancer through the immune system.
In follow-up to our preliminary work, there is the possibility that HS mutation (i.e., under-sulfation) facilitates direct antigen presentation to during DC-effector T-cell interactions at the immunologic synapse within tumors. A variety of antigen presentation studies are planned using tumor DCs from CD11cCre(+) Ndst1f/f mutant mice, with comparison to that of Cre(-) controls. These are important upcoming studies since we have not tested either tumor DCs or this specific unique mutation-context in this platform yet.