Microglia are the resident macrophages of the brain. They are abundant in brain tumors and likely have multiple functions. In the right context, microglia can be phagocytic and ingest treated tumor cells. We are investigating a novel regulatory mechanism of microglia proliferation and function to increase clearance of drug-treated tumor cells. The ultimate goal of this project is to leverage phagocytic microglia to induce more tumor regression with drug therapy so that greater tumor control can be achieved.
Pairing radiation with check point inhibitors has increased the efficacy of radiation in some tumor types, but this strategy is not successful with brain tumors. This is likely the result of multiple immune suppressive mechanisms within the brain tumor that dampens the ability of the adaptive immune cells, such as cytotoxic T cells, to aid in tumor cell killing. With this project, we are studying how different types of myeloid cells, monocyte derived macrophages, dendritic cells, and neutrophils recruited to the tumor after radiation can impact the activity of anti-tumor T cells. The goal of this project is to identify reversible myeloid cell-based mechanisms that hinder the function of T cells. Once identified, we will reverse these mechanisms to bolster the efficacy of radiation for the treatment of pediatric brain tumors.
Radiation is an essential treatment modality for many pediatric brain tumor types. While radiation damages tumor cells, it can also harm normal brain tissue. As a result, patients who receive radiation can have long-term neurologic problems such as neurocognitive deficits and damage to blood vessels that can lead to strokes. Recent works by others have shown that a new modality of radiation delivery called FLASH whereby the velocity of particle delivery is increased, spares normal brain tissues of the damage typically associated with delivery using conventional velocity. This suggests that children have the most to gain from the neuroprotective property of FLASH as long as tumor killing efficacy is at least equal to conventional therapy. In a collaboration of radiation oncologist. Dr. Stephanie Perkins and radiology professor, Dr. Buck Rogers, and their team, we are studying whether FLASH radiation has the same efficacy as conventional radiation in controlling medulloblastoma growth. We are also interrogating the intra and extra-tumoral immune response to each modality.