Medulloblastoma Immune Microenvironment Resembles Early Brain Development and Reveals Novel Basophil-B Cell Associated Signatures

Background Medulloblastoma is the most common malignant pediatric brain tumor, yet the mechanisms underlying immune evasion remain poorly understood. Since the developing brain’s immune environment naturally promotes tissue tolerance and remodeling, we hypothesized that medulloblastoma may exploit developmental immune programs to escape surveillance. Here, we aimed to characterize the immune microenvironment of medulloblastoma compared to healthy brain tissue across different developmental stages. Methods We analyzed RNA-sequencing data from 124 medulloblastoma tumors and 47 control brain samples spanning post-conception weeks 8–37 through adulthood. Using xCell and DeconRNAseq, we quantified enrichment scores for 34 immune cell types and compared their profiles. Results Medulloblastoma tumors exhibited a distinct immune profile most similar to post-conception week controls among all age groups tested (P < .001). Key findings included significantly elevated basophils, neutrophils, immature dendritic cells, memory B cells, Th2 cells, and NKT cells in medulloblastoma samples. Conversely, macrophages (M1 and M2 subtypes), matured dendritic cells, regulatory T cells, and most B cell populations showed reduced enrichment. This pattern suggests a Treg-independent immunosuppressive mechanism. Notably, basophil enrichment in medulloblastoma was comparable to post-conception week samples but significantly higher than older controls, potentially explaining the concurrent elevation of memory B cells. Conclusions Medulloblastoma displays an immune microenvironment resembling early developmental stages, characterized by elevated basophils and memory B cells alongside reduced conventional immune surveillance mechanisms. These findings suggest that medulloblastoma may co-opt developmental immune tolerance programs and highlight basophil-B cell interactions as potential therapeutic targets. The developmental similarity provides new insights into medulloblastoma pathogenesis and immune evasion strategies.