Blocking the CD47-SIRPα axis by delivery of anti-CD47 antibody induces antitumor effects in glioma and glioma stem cells.

Tumor initiating cells or cancer stem cells (CSCs) play an important role in the initiation, development, metastasis, and recurrence of tumors. However, traditional therapies have limited effects against CSCs and targeting these cells is crucial when developing new therapeutic strategies against cancer. One potentially targetable factor is CD47, a member of the immunoglobulin superfamily. This protein acts as an anti-phagocytic "don't eat me" signal and is often found expressed by cancer cells, particularly CSCs. CD47 functions by activating signal regulatory protein-alpha(SIRP-alpha) expressed on macrophages, preventing phagocytosis. However, the role of CD47 in glioma stem cells (GSCs) has been not been thoroughly investigated. Our study therefore examined the expression and function of this protein in glioma cells and GSCs. We found that CD47 was highly expressed on glioma cells, especially GSCs, and that expression associated with worse clinical outcomes. We also found that CD47+ glioma cells possessed stem/progenitor cell-like characteristics and knocking down CD47 expression resulted in a reduction in these characteristics. Treatment with anti-CD47 antibody led to increased phagocytosis of glioma cells and GSCs by macrophages. We next examined the effects of anti-CD47 antibody on glioma cells/GSCs in an immune competent mouse glioma model, revealing significant inhibition of tumor growth and prolonged survival times. Importantly, there were no apparent side effects in the animal model. In summary, we have shown that CD47 is a potentially safe and effective therapeutic target for glioma.