Immunosuppressive microenvironment characterizes high-grade pediatric CNS malignancies and correlates with poor survival. (A) For abundant diagnosis types in the CBTN cohort, the frequency of immune subtypes stratified by diagnosis is shown for the primary samples, coded as per the TCGA classification. The distribution of immune subtypes differs between high- and low-grade lesions (X2 = 129.1, p-value < 1–16), and residuals reveal a higher contribution of C4 among high-grade tumors and a higher contribution of C3 among low-grade tumors. (B) A univariate Kaplan–Meier curve correlates the C4 immune subtype with the worst prognosis, whereas C3 demonstrates a favorable prognosis (log rank, p < 0.001). (C) A multivariate Cox regression model was fitted to determine the immune subtype effect on survival after adjusting for tumor grade, extent of neurosurgical resection, and age. Relative to C3, both C4 (4.66, p = 0.003) and C5 (3.49, p = 0.034) subtypes exhibit an increased hazard ratio (HR) for overall survival (OS).