Azadeh Kiumarsi

and 7 more

Pediatric gliomas represent a group of tumors that arise from glial cells within the central nervous system (CNS) and account for approximately 25% of pediatric cancers. If not completely eradicated, these tumors can lead to significant complications, resulting in disabilities and complex disorders in adulthood. Current therapeutic approaches for gliomas often fall short, with tumor recurrence being a common outcome. The substantial burden of disability-adjusted life years (DALY) associated with gliomas, combined with the limited effectiveness of existing treatment strategies, has prompted researchers to explore alternative therapies. Immunotherapy has emerged as a promising modality in the management of pediatric gliomas. Given that conventional treatments—including surgical intervention, standard chemotherapy, and radiotherapy—often yield suboptimal outcomes, immunotherapy offers a compelling alternative for inhibiting the rapid proliferation of glioma cells. A comprehensive understanding of the immune microhabitat within pediatric gliomas is critical for elucidating the potential effectiveness of immunotherapeutic and immune cell therapy approaches. Insights into the tumor-associated immune environment can inform the optimization of these therapies by revealing mechanisms of immune evasion and potential targets for intervention. One area of particular interest is natural killer (NK) cell therapy, which has shown promise in targeting pediatric gliomas. This review aims to synthesize recent research findings on the mechanisms by which NK cells interact with glioma cells, emphasizing key preclinical and clinical studies that highlight both the potential advantages and challenges of this therapeutic approach. We will examine the immunological interactions between NK cells and glioma cells, strategies to enhance NK cell effectiveness, and the potential for combining NK cell therapies with other treatment modalities. Furthermore, this review will discuss the safety and tolerability of immunotherapeutic interventions within the pediatric population to inform future research and clinical practices in the management of pediatric gliomas. By integrating findings from existing literature, we aim to provide a holistic perspective on pediatric glioma’s immune microenvironment, emphasizing the potential of immune-based therapies as part of a comprehensive treatment strategy.