Stem cells ‘also suppress immune response’

The cancer stem cells that initiate glioblastoma multiforme also suppress an immune system attack on the disease, according to scientists from the MD Anderson Cancer Center, Texas, US.

Glioblastoma stem cells have been implicated in tumour resistance to chemotherapy and radiation, and are believed to be responsible for the relentless recurrence of the disease. The researchers said their work uncovers “an important mechanism” explaining why glioblastoma – and cancer patients in general – have impaired immune responses. Senior author Amy Heimberger said: “The cancer stem cells inhibit T cell response, and it is these T cells that recognise and eradicate cancer”

The researchers defined cancer stem cells as those which expressed the CD133 marker, formed neurospheres in culture, and recreated glioblastoma multiforme when injected into the brain of a mouse. They also had to be capable of differentiating into neurons, astrocytes and glial cells.

The research demonstrated that the stem cells have a three-pronged attack on T cell response. They markedly inhibited T-cell proliferation and activation, induced regulatory T cells which act as brakes on the immune response, and triggered T-cell apoptosis that was mediated by B7-H1 and soluble Galectin-3.

The immunosuppressive effect was reversed when the team placed undifferentiated glioma stem cells into a culture medium that caused them to differentiate into the 3 types of neural cell (Clin Cancer Res 2010; 16 (2): 461-73).

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

“Now we have to be cognisant 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.”