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Cancer stem cells suppress immune response against brain tumor
Date:1/15/2010

li>Killing T cells via apoptosis, or programmed cell suicide. This is accomplished via the immunosuppressive protein B7-H1 in the stem cells directly contacting the T cells or by secretion of Galectin-3.

Wei said this immunosuppressive effect was reversed when the team placed the undifferentiated glioma stem cells in a culture medium that causes them to differentiate into the three types of neural cell.

"There are multiple research groups around the country, including ours, trying to develop vaccines or other immunotherapeutics against glioma stem cells," Heimberger said. "Now we have to be cognizant that the stem cell may deliver a fatal blow back to the immune system, which will help us understand how to design immune-based therapies."

New drugs or combination therapies are needed, because after decades of research, little progress has been made in treating glioblastoma multiforme. With the best of care patients survive an average of 14 months.

STAT3 pathway inhibits T cell response

In a separate paper in the Jan. 15 issue of Molecular Cancer Therapeutics, the research team also reports that the STAT3 signaling pathway is highly active in glioblastoma stem cells and suppresses immune system response.

Heimberger said the STAT3 molecule is known to induce cancer proliferation and survival migration and invasion, growth of new blood vessels, and immunosuppression.

Inhibiting STAT3, either by silencing it with small interfering RNA or by treatment with an experimental drug called WP1066, reactivates the immune response.

"We showed that if you treat the cancer stem cells with an inhibitor of STAT3, you can restore T cell proliferation and the ability of those cells to make pro-inflammatory cytokines," Heimberger said.

While the response is powerful it is not complete, so the researchers conclude there a STAT3-independent pathway is also at work in mediating immune suppression.
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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