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Rare immune cell is key to transplant's cancer-killing effect

ANN ARBOR, Mich. Researchers at the University of Michigan's Comprehensive Cancer Center have discovered the secret weapon behind the most powerful form of cancer immunotherapy known to medicine.

Scientists call it the graft-versus-leukemia effect, and it occurs when new immune cells from donated bone marrow, called the graft, attack malignant cells in the patient and destroy them. This intense immune reaction between donor and host cells, which follows a bone marrow transplant from a healthy donor, has saved the lives of thousands of patients with leukemia, lymphoma and other types of blood and immune system cancers.

In a study to be published Oct. 16 in the advanced online edition of Nature Medicine, U-M scientists describe how antigen presenting cells are crucial to graft-versus-leukemia's cancer-killing effect.

The discovery is significant, because it could help make cellular immunotherapy safer, more effective and an option for more cancer patients especially those for whom a donor is unavailable or those who cannot tolerate the procedure's side-effects.

"We already knew that donor T cells were important for an effective GVL response, but now we know there's another cell the antigen presenting cell or APC which plays a critical role in the process," says James L.M. Ferrara, M.D., who directs the U-M Cancer Center's Blood and Marrow Transplant Program.

Antigen presenting cells are rare immune system cells, which look something like a starfish. Their job is to digest proteins called antigens from foreign cells or pathogens and present them to T cells. This alerts the immune system to prepare to fight the invader. When APCs present cancer cell proteins to T cells, the T cells are primed to attack the cancer.

"We found that without functional APCs to process and present antigens to T cells, there is no graft-versus-leukemia response, and the cancer is likely to return," says Pavan R. Reddy, M.D., an assistant
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