Sara Mohammad T Althaqafi

Bioinformatics Specialization · Cohort 2026

Micro Cells, Macro Variability: An Exploratory Single-Cell Analysis of Myeloid Ontogeny and T Cell Functional Heterogeneity in Pediatric High-Grade Glioma

Pediatric high-grade glioma (pHGG) is an aggressive childhood malignancy with poor prognosis and limited response to immunotherapy. With recent literature affirming that pediatric gliomas are molecularly distinct from adult glioblastoma, immune mechanisms established in adults may not translate directly to this setting. The pHGG immune microenvironment is dominated by myeloid cells spanning a developmental continuum from resident microglia to recruited macrophages, but whether this ontogeny axis governs immunosuppressive function remains contested. We analyzed single-cell RNA- sequencing data from the ScPCA pediatric glioma cohort (SCPCP000001, n = 23), using literature-curated marker panels for myeloid lineage, immunosuppressive/scavenger state, CD8+ exhaustion, and cytotoxicity. CD8+ T cells were identified by CD8A expression, and scores were computed using AUCell and cross-validated against UCell. Myeloid ontogeny was not significantly associated with immunosuppressive state at the patient level (Spearman’s rho = -0.26, p = 0.34, n = 15), consistent with a non-binary model of pHGG myeloid identity, although the modest sample size limits power. Within the CD8+ compartment, the dispersion of cytotoxicity scores differed significantly across patients (Levene’s F = 5.95, p = 5.1 × 10−8), whereas exhaustion-score dispersion did not (F = 0.72, p = 0.69), indicating distinct patterns of patient-level heterogeneity across these two transcriptional programs. Myeloid immunosuppressive score was also significantly higher in chemotherapy-exposed patients (Wilcoxon W = 4, p = 0.007). Together, these exploratory findings suggest that functional cytotoxicity and checkpoint-associated exhaustion may capture different dimensions of the pHGG CD8+ immune state and support further investigation of both axes in larger pediatric cohorts.

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