The anti-tumor immune microenvironment in the Sonic Hedgehog subclass of medulloblastoma
Medulloblastoma is the most common solid pediatric tumor and the leading cause of cancer death among the pediatric patients. Current treatment options result in about a 70% survival rate, but many survivors are afflicted with life-long side effects and greatly reduced quality of life. Therefore, the search for novel, less toxic, and more effective treatment options is currently occupying the minds of pediatric cancer researchers. Recently it was shown that in the human Sonic hedgehog subgroup of medulloblastoma there is high infiltration of a unique type of immune cell - macrophages. We decided to investigate their role in the medulloblastoma context and discovered a surprising phenomenon. Contrary to the pro-tumoral role seen in the common adult brain malignancy glioblastoma, macrophages in medulloblastoma play an anti-tumoral role.
Project Goal: Our preliminary experiments confirmed macrophage toxicity to tumor cells both in tissue culture and in animals. In this proposal we seek to characterize the anti-tumoral properties of macrophages to further understand how they enhance tumor cell death, in a mouse medulloblastoma model, and to determine whether they have similar properties in other mouse medulloblastoma models. This approach will give further insight as to how effectiveness of immunotherapies may depend on the genes and pathways that drive each subtype of tumor.
Project Update 2023: We have studied the role of IGFBP2 in regulating proliferation and migration of medulloblastoma cells of the Sonic hedgehog molecular subgroup, using cell cultures derived from these tumors. The data we obtained laid the groundwork for an NIH R01 submission, to study IGFBP2 in vivo using genetically engineered mouse models.
