Expression patterns of carbonic anhydrase IX and immune response biomarkers in pediatric gliomas and glioneuronal tumors

PURPOSE: Carbonic anhydrase IX (CAIX), a hypoxia-induced enzyme, contributes to tumor acidosis and may modulate antitumor immunity. Its role in pediatric central nervous system (CNS) tumors remains poorly understood. This study examined CAIX and immune biomarker expression in pediatric gliomas and glioneuronal tumors (GNTs) and their associations with clinical outcomes. METHODS: CAIX and selected immune biomarkers were evaluated using immunohistochemistry in 34 pediatric patients (ages 0-17 years) with low-grade gliomas (LGGs; n = 21), GNTs (n = 6), and high-grade gliomas (HGGs; n = 7). RESULTS: CAIX was expressed in 58.8% of tumors, with no statistically significant difference between the combined LGG/GNT and HGG groups. CD3 (87.9%), CD8 (81.8%), CD44 (93.9%), CD68 (100%), CD163 (75.8%), and CCR2 (69.7%) were the most frequently detected biomarkers, whereas PD-L1 (15.2%), PD-1 (0%), and CD206 (24.2%) were rarely detected. CAIX correlated positively with CD44 (p = 0.01) and CD206 (p = 0.009). Strong CD68 expression (> 30%) was associated with significantly better 2-year event-free survival (EFS) than lower expression (91.7% vs. 53.8%; p = 0.011). No significant associations between EFS and CAIX or other immune biomarkers were observed (all p > 0.05). CONCLUSION: Pediatric gliomas and GNTs frequently express CAIX and monocyte/macrophage-related biomarkers but exhibit a low immune checkpoint profile (PD-1 and PD-L1). Unlike findings from adult studies, CAIX was neither enriched in HGGs nor associated with a worse prognosis. Strong CD68 expression may represent a candidate target for combination therapeutic strategies, although validation in a larger, homogeneous pediatric CNS tumor cohort is needed.