Children's National researchers discover a mechanism of tumor ganglioside inhibition of killer T-cells
WASHINGTON, DC— A multi-disciplinary research team at Children’s National Health System has identified gangliosides as another piece in the puzzle around why the body’s natural immune system, led by CD8+ T-cells, or “killer white blood cells,” is unable to effectively combat tumors.
In a joint research study published in the Journal of Immunology, the team from the Immunology Initiative of the Sheikh Zayed Institute for Pediatric Surgical Innovation and the Center for Cancer and Immunology Research at Children’s National Medical Center found that the gangliosides shed by tumor cells inhibit T-cells function. Gangliosides are a constituent of all cells, but are shed in tremendous amounts by tumor cells as they grow and divide. They have been shown in previous studies to have inhibitory properties, but scientists have never before definitively shown how they diminish the function of the CD8+ T-cells.
One key way in which CD8+ T-cells combat foreign cells in the body is through lytic granule release and exocytosis. These lytic granules are directed from the T-cell to the foreign body, attach to it, and begin to destroy it. However, this study identified that the gangliosides shed by the tumor appear to prevent these lytic granules from targeting the tumor and attaching to the cancerous cells.
“This is an example of how breakthroughs come from collaboration,” said Sasa Radoja, PhD, principal investigator in the Immunology Initiative of the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National. “No one had looked specifically at how gangliosides impact these T-cells. When we asked the question, however, we were lucky enough to have one of the world’s leading experts in gangliosides and former Scientific Director of the Children’s Research Institute, Stephan Ladisch, MD, just down the hall here at Children’s.”
Dr. Radoja’s lab specializes in understanding how tumors are able to “cloak” themselves and avoid detection and destruction by the body’s immune system. The lab focuses on identifying the complex series of reasons why, but also on finding ways to make the immune system smarter and stronger so it can more effectively fight these tumors.
“Our next step with these results is to find a way to alter CD8+ T-cells so they are not susceptible to these inhibitors,” Dr. Radoja continued. “This study helps us understand exactly how the T-cells are affected on a molecular level, which we need to know in order to find a way to work around the mechanism.”
Contact: Jennifer Stinebiser, 202-476-4500