Graduate Student Duke Univ. Sch. of Med., United States
Introduction/Rationale: Oligodendrogliomas frequently recur despite standard therapy, but how the immune microenvironment evolves during recurrence remains poorly understood.
Methods: Visium Spatial Transcriptomics data from primary and matched recurrent oligodendrogliomas from 14 patients were processed using SpaceRanger and deconvoluted with SpaCET’s low-grade glioma model to estimate cell-type proportions. Cell-type fractions were normalized using Centered Log-Ratio transformation and clustered (k = 5, Euclidean distance) to define reproducible spatial niches. Immune subset distributions were compared between primary and recurrent tumors to assess niche-specific remodeling, with propensity score matching applied to control for baseline clinical and molecular differences between treated and untreated patients.
Results: Five spatial niches were identified, including immune-enriched perivascular and infiltrative regions. Recurrent tumors showed marked loss of adaptive immunity, with downregulation of CD4⁺ T-helper subsets (Th1, Th2, Th17, Tfh; log₂FC ≈ –3) and total CD4⁺ T cells (–2.9). This loss, most pronounced after radiation and/or chemotherapy, indicates therapy-associated collapse of adaptive immune niches. Macrophage and microglial populations were preserved or increased, reflecting a shift toward a myeloid-dominant, immunosuppressive microenvironment. Immune-rich perivascular regions exhibited depletion of T-helper diversity and enhanced myeloid signaling, consistent with immune exclusion and vascular remodeling. These findings persisted after propensity score matching, with treated tumors remaining enriched for immunosuppressive niches (p < 0.05). Validation by Xenium spatial transcriptomics and CODEX multiplex imaging will be included in the final presentation.
Conclusion: Recurrent oligodendrogliomas exhibit collapse of adaptive immune niches and expansion of myeloid-dominant regions, defining immune remodeling as a hallmark of recurrence and myeloid-driven immunosuppression as a potential therapeutic target.
