In recent years, neuroglioma has been a common malignant tumor among pediatric brain tumors, drawing our research focus. Considering the immune regulation role of Omega-6 fatty acids and their metabolites, this study examined arachidonic acid metabolite prostaglandin D2 (PGD₂) in tumor and immune cell interactions. Using real-time cell analysis (RTCA) and luciferase assays, we evaluated Omega-6-related compounds' effects on glioblastoma cells and natural killer cells (NK-92). Celecoxib, a COX-2 inhibitor, significantly increased tumor cell lysis and activity, promoting tumor death. Celecoxib derivative 038 had limited tumor effects but inhibited NK-92 proliferation. PGD₂ suppressed NK-92 cell cytotoxicity, suggesting its role in tumor immune evasion. These findings support targeting Omega-6 metabolism pathways for brain tumor immune regulation and aid nutrition-based treatment strategies.