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Leukemia cells evade immune system by mimicking normal cells, Stanford studies show
Date:7/23/2009

n Jaiswal killed off the macrophages in mice, it allowed even the low-CD47 cell line to cause disease.

All told, the evidence points toward macrophages playing a starring, and unexpected, role in destroying cancer cells. Part of what's called the innate immune system, macrophages and other protective cells cruise the body looking for all types of trouble. In contrast, the adaptive immune system mobilizes specialized T and B cells in response to specific activation signals.

"We hypothesized that, if elevated CD47 expression renders the leukemia stem cells invisible to the innate immune system, human patients with elevated levels would fare more poorly than those with lower levels," said Majeti. "Furthermore, if we could prevent that interaction between the cancer cells and the macrophages, maybe the cells would get eaten."

In fact, in three independent, previously published data sets comprising 664 human patients, those whose acute myeloid leukemia cells express higher levels of CD47 were about twice as likely to die from the cancer within a certain time period than those whose cancers expressed lower levels of the molecule: High CD47 expressors lived for a median of 9.1 months, while low CD47 expressors lived for a median of 22.1 months.

In further study of the high-CD47 expressing cancer stem cells in a culture dish, researchers added an antibody that blocks the interaction of the cancer cells with macrophages essentially hiding the protective badge. This allowed the macrophages to engulf the cancer cells. A similar treatment in mice inhibited the human cancer cells' ability to cause leukemia and even prolonged the survival of mice with previously established leukemias.

"This was the real kicker," said Majeti. "These mice showed a profound clinical response." Majeti and his colleagues are now planning to craft a similar antibody for use in human clinical trials.

Although the therapeutic promise is exciting, oth
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Contact: Ruthann Richter
richter1@stanford.edu
650-725-8047
Stanford University Medical Center
Source:Eurekalert

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