Novel therapies are desperately needed for pediatric solid tumors, where more than 30% of patients die from their disease. Immunotherapies offer significant potential to meet this need, but this potential has not yet been realized in children. Immune checkpoint inhibitors (ICIs), a type of immunotherapy, have shown success in many adult cancers but rarely work for children. This is partly because pediatric tumors have fewer mutations than adult tumors. To the immune system, fewer mutations mean pediatric tumors appear more similar to healthy tissue, making it harder for the immune system to attack the cancer while sparing healthy cells. In addition to differences in tumors, children’s immune systems are different from adults, often skewing toward tolerance and reduced activity, which helps prevent autoimmunity but may limit the effectiveness of cancer immunotherapies. Unfortunately, how this immune system immaturity contributes to poor responses to ICIs remains unknown.