By Chris Porter, MD
Aflac Cancer & Blood Disorders Center of Children’s Healthcare of Atlanta
Researchers have learned a great deal about how the human immune system can function as physiologic superheroes – able to prevent and cure diseases, including cancer. Like particularly cunning comic book villains, some cancers devise intricate plans to weaken their superhero foes – think kryptonite to Superman. In our lab, we have been investigating how blood cancer cells evade the immune system and have discovered that the cancer cells use a molecular kryptonite, called Siglec15, to weaken the immune cells. Fortunately, there may be ways to shield our immune cells and new ways to strengthen them, which we are actively pursuing every day.
Cancers derived from blood cells, including leukemia and lymphoma, are the most common cancers in children. Thanks to research, cure rates are better than ever. But cancer remains the leading cause of illness-related death in children. Thus, there is a need for better therapies, and understanding how cancer cells behave is critical to developing better medicines.
A couple of years ago, our lab found that leukemia cells depend on a protein called calcineurin to evade immune cells. In the cell, calcineurin helps control the expression of a number of other proteins. One of the proteins that calcineurin controls is a signaling molecule, IL-12. This molecule is a member of a family of signaling proteins called cytokines. Researchers have known for a long time that IL-12 very strongly stimulates immune cells to kill cancer cells. However, IL-12 has not been an effective therapy, in part because it can cause several side effects. To get around this problem, we are collaborating with scientists at Emory University and the Georgia Institute of Technology. Together we hope to develop a nanomedicine to deliver IL-12 exactly to where it needs to be, where immune cells interact with cancer cells. This will effectively give additional super-powers to help the immune cells eliminate the cancer cells.
In addition, we found that calcineurin controls the expression of Siglec15, a protein of which not much is known. Leukemia and lymphoma cells seem to make a lot of Siglec15, which we know can inhibit immune cells. In fact, children with leukemia have much higher levels of Siglec15 in their blood than healthy individuals. Now we are trying to understand how the leukemia and lymphoma cells make it and how it inhibits the immune cells. In addition, we are working with a drug company that makes a medicine that can block Siglec15, which could act as a forcefield for the immune cells.
Thus, with funding from CURE, we are making great strides in figuring out ways to strengthen and protect immune cells, which should let these superheroes destroy the villainous cancer cells.