Max Wintermark, MD, MS, MBA

Medulloblastoma (MB) is the most common malignant brain tumor in children. While treatments like surgery, radiation, and chemotherapy are standard, they often lead to severe long-term side effects, especially in developing brains. Despite advances in classifying MB into molecular subtypes—Wingless (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4—therapeutic progress has been slow, particularly for the SHH and Group 3/4 subtypes, which tend to have poor outcomes.

This research explores the potential of natural killer (NK) cell immunotherapy as a novel treatment option for MB. NK cells are part of the immune system that can attack cancer cells without the need for specific antigens, making them promising for pediatric cancers, which typically have fewer mutations. However, MB tumors create a hostile environment for NK cells, partly due to autophagy, a process that helps tumor cells survive under stress and develop resistance to NK cell therapy.

The study aims to improve NK cell therapy by blocking autophagy pharmacologically, which may sensitize MB tumors to immunotherapy.

This work is innovative in several ways: it seeks to make MB tumors more susceptible to immune-based treatments, and introduces a new imaging method for monitoring NK cells in the brain. If successful, this strategy could offer a new, less toxic option for treating recurrent or hard-to-treat MBs, improving outcomes for children who have limited options with existing treatments.