Central nervous system immunological complications of immunotherapy in pediatrics

Introduction: Immunotherapies such as CAR T-cell therapy and immune checkpoint inhibitors (ICIs) have transformed pediatric cancer treatment but are increasingly associated with severe central nervous system (CNS) immune-related adverse events (irAEs), which remain poorly understood in children. Areas covered: This review summarizes current knowledge on CNS irAEs in children receiving CAR T-cells, ICIs, and monoclonal antibodies. Based on a narrative literature review from PubMed, Scopus, and Web of Science (2010–2025), it focuses on pediatric neurotoxicity, immunopathogenesis, and age-specific vulnerabilities, including an immature blood-brain barrier, reduced naive T-cells, and chronic inflammation. Common irAEs include ICANS, autoimmune encephalitis, Guillain-Barré syndrome, and hypophysitis. Expert opinion: Managing CNS immune toxicity in pediatric immunotherapy is a critical challenge that requires early detection, ongoing monitoring, and age-appropriate interventions. Progress depends on identifying predictive biomarkers and tailoring immunomodulatory strategies to enhance safety while preserving efficacy.