Re-engineering the Tumor Microenvironment in DMG

Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas are aggressive childhood brain tumors with very few effective treatment options. These tumors grow in parts of the brain that cannot be safely removed, and most medicines cannot reach them because of the brain’s natural protective barriers. Even when treatments do arrive at the tumor, the surrounding environment is filled with immune cells that have been “switched off” and cannot help fight the cancer. These challenges have made it difficult to develop new therapies.

My research team is working on ways to deliver treatments directly to the tumor and to “wake up” the immune cells that live there. We use extremely small particles—similar to those used in some vaccines—to carry medicines into the fluid around the brain and spinal cord. Our early studies show that by adjusting how these particles are made, we can guide them to different types of cells inside the tumor. In this project, we will first identify which particle designs are best at reaching tumor cells versus the immune cells that surround them. This will help us understand how to target future treatments more precisely. At the same time, we will test a new approach that delivers a natural immune-boosting signal directly to microglia, the brain’s resident immune cells. We will also see whether combining this immune-activating strategy with an existing chemotherapy drug improves its effectiveness. Overall, this work aims to create tools that make it easier to reach and influence the tumor environment in DIPG/DMG. The knowledge gained could support the development of safer, more targeted combination treatments for children facing these challenging cancers.