Efficacy of Activated Myeloid Cells lacking NF-kB p50 for Glioblastoma
Mentor: Alan Friedman
Glioblastoma (GBM) is a pediatric brain tumor that demonstrates some of the lowest survival rates among all pediatric malignancies. Malignant GBM cells secrete hormones that attract normal immune cells called macrophages, which in turn support tumor growth and aggressiveness through the secretion of growth factors and other signaling molecules. Given their role in promoting tumor progression, these tumor-associated macrophages are a target for anti-cancer therapies. Other investigators have blocked the specific hormones secreted by GBM cells as a means to prevent macrophage recruitment, but tumors quickly circumvented this blockade by simply secreting alternative hormones. Previously, the Friedman laboratory sought to influence macrophage recruitment through the inhibition of NF-kB p50, a protein that controls the activity of genes within macrophages. Mice that lacked NF-kB p50 demonstrated significantly slower GBM growth and longer overall survival relative to mice possessing the protein. However, most strikingly, the absence of NF-kB p50 was found to reprogram tumor-associated macrophages to attract and activate tumor T cells to attack and destroy the tumor as opposed to supporting its survival. These findings demonstrate the potential of NF-κB p50 inhibition as an anti-cancer agent.
