Defining how unique properties of the pediatric immune system contribute to poor efficacy of checkpoint blockade in children
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.
Project Update 2025:
To address this, we will use a new “cancer organoid” model to study how children’s immune cells respond different to cancer and ICI therapy, compared to adults. We will examine how age impacts immune responses to ICIs, how the type of cancer target affects these responses, and uncover the molecular reasons why children’s immune cells may not respond well to ICIs. Ultimately, this research will define how the immune system recognizes and regulates responses to pediatric cancers to inform the development of safer and more effective immunotherapies for children with cancer.
