Glioblastoma multiforme (GBM) has a dismal survival and cancer-initiating cells have been shown to recapitulate the characteristic features of GBM including mediating chemotherapy and radiation resistance. We isolated cancer-initiating cells from GBM patients and found that they inhibited T cell proliferation and activation, induced regulatory T cells, triggered T cell apoptosis and recruit and polarize the MFs/microglia to become immunosuppressive (M2).The immunosuppressive properties were reversed when STAT3 is blocked. In mice that co-express PDGF-B + Bcl-2 or STAT3 under the control of the glioneuronal-specific Nestin promoter, the high-grade gliomas that develop had a marked intratumoral influx of macrophages influenced by tumor STAT3 expression and were a negative prognosticator. In mice with gliomas treated with the STAT3 blockade agent, WP1066, there was a marked increase in survival time. Blockade of the STAT3 pathway with agents such as WP1066 would be a compelling approach for treating malignant gliomas

Glioma-associated cancer-initiating cells induce immunosuppression

242nd National Meeting (2011)

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