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Cancer Stem Cells Suppress Immune Response in Glioblastoma

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Malignant brain tumors express a number of antigen targets that should attract a hostile immune response, but they evade this attack by suppressing the immune system.

In two papers published Friday, M. D. Anderson researchers identify culprit mechanisms employed by glioblastoma multiforme to disable the immune system.

CCR cover_0110.jpgA report featured on the cover of Clinical Cancer Research demonstrates that a subset of tumor cells called cancer-initiating cells disables immune system T cells that otherwise would recognize and eradicate cancer. These tumor cells, also called cancer stem cells, thwart detection by killing T cells, converting them into a type of T cell that actually slows immune response and by producing molecules that block T cell response.

The team also found a way to reverse this immune suppression. The cancer stem cells are capable of converting themselves into one of three types of brain cell: neurons, astrocytes and glial cells. First author Jun Wei, Ph.D., instructor in the Department of Neurosurgery, explained that immunosuppression is reversed if the stem cells are forced to convert to one of the three types of brain cell.  

In a companion paper in Molecular Cancer Therapeutics, the same research team shows that the STAT3 signaling pathway is highly active in glioblastoma stem cells and suppresses immune system response.

"We found 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," says senior author Amy Heimberger, M.D. professor in the Department of Neurosurgery. Research continues on how the inhibitors work, and whether they cause the stem cell differentiation that the team has shown reverses immune suppression.

Read the News Release - Cancer Stem Cells Suppress Immune Response Against Brain Tumor 

"There are multiple research groups around the country, including ours, trying to develop vaccines or other immunotherapeutics against glioma stem cells," Heimberger says. "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."

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