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Certain cancer therapies' success depends on presence of immune cell, Stanford study shows in mice
Date:10/27/2010

les secreted by immune cells. These molecules, called cytokines, relay instructions to other cells in the area to coordinate the body's response to infection or disease. Felsher and his colleagues found that the expression levels of many cytokines varied between the wild-type mice and those with compromised immune systems. One in particular, a molecule called thrombospondin-1, was especially interesting. It is produced by CD4-positive T cells, and it regulates angiogenesis.

"We knew that if we replaced CD4-positive cells in immune-compromised mice, we repaired their ability to reject the tumors when Myc was inactivated," said Felsher. "When we tried the same experiment with CD4 cells that couldn't express thrombospondin, the mice couldn't reject the tumor."

Therefore, the presence of thrombospondin is important to the process of tumor rejection caused by oncogene inactivation. Felsher and his colleagues saw a similar effect in a mouse model of another type of leukemia that is dependent on the expression of different oncogenes, suggesting that their findings may translate to other instances of oncogene addiction. They also showed that wild-type mice treated with an immune suppressor called cyclosporine A (commonly used in human organ transplant recipients to prevent rejection) had a similar effect on angiogenesis and the ability of the tumor cells to enter senescence.

"The problem is, many treatments for patients with lymphoma and leukemia attack both the cancer cells and the immune system," said Felsher. "So we really have to think about this. We can't assume that therapies that target oncogenes act independently of the rest of the body. They may depend on an intact immune system."

Although many patients believe that their immune systems are inherent cancer fighters, it's not always the case, said Felsher. Rather, most cancers occur and progress in the presence of the immune system, each shaping the other. Under some conditions th
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Contact: Krista Conger
kristac@stanford.edu
650-725-5371
Stanford University Medical Center
Source:Eurekalert

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