Dissecting the immune landscape in pediatric high-grade glioma reveals cell state changes under therapeutic pressure.

Abstract

Pediatric high-grade gliomas (pHGGs) are among the most lethal childhood tumors. While therapeutic approaches were largely adapted from adult treatment regime, significant biological differences between pediatric and adult gliomas exist, which influence the immune microenvironment and may contribute to the limited response to current pHGG treatment strategies. We provide a comprehensive transcriptomic analysis of the pHGG immune landscape using single-cell RNA sequencing and spatial transcriptomics. We analyze matched malignant, myeloid, and T cells from patients with pediatric diffuse high-grade glioma (HGG) or high-grade ependymoma, examining immune microenvironment distinctions after chemo-/radiotherapy, immune checkpoint inhibition treatment, and by age. Our analysis reveals differences in the proportions of pediatric myeloid subpopulations compared to adult counterparts. Additionally, we observe significant shifts toward immune-suppressive environments following cancer therapy. Our findings offer valuable insights into potential immunotherapy targets and serve as a robust resource for understanding immune microenvironmental variations across HGG age groups and treatment regimens.