Predicting and Overcoming Resistance to Immunotherapy in Pediatric High-Grade Glioma

Immunotherapy has emerged as a powerful approach to treating cancer, but only a subset of patients respond, and the remainder suffer severe side effects without benefiting from the therapy. There is a critical need to understand the factors that limit success of this approach, and to develop strategies to enhance responsiveness. Most immunotherapies involve killing of tumor cells by cells of the immune system called 'T cells'. For T cells to attack tumors, the tumors must have a protein called MHC on their surface; if tumor cells have no MHC, they cannot be targeted by T cells. Our work focuses on immunotherapy for pediatric high-grade gliomas (pHGG), the leading cause of death in children with brain tumors. We recently identified a mutation that leads to loss of MHC on pHGG cells. Tumors that carry this mutation are invisible to immune cells and insensitive to many immunotherapy approaches.