Abstract 6212: Spatial immune and vascular remodeling defines recurrence in oligodendroglioma

Abstract Introduction/Rationale: Oligodendrogliomas recur after therapy but how spatial immune architecture changes during recurrence is poorly understood. Methods: Visium Spatial Transcriptomics (ST) from primary and matched recurrent tumors (n = 14 patients) were processed with SpaceRanger. Cell-type deconvolution was performed using SpaCET’s low-grade glioma model, generating spatial immune and stromal distributions. Cell-type fractions were normalized using Centered Log-Ratio transformation and clustered (k = 5, Euclidean distance) to define niches. Immune subsets were compared to assess niche-specific remodeling. Propensity score matching was used to control for baseline differences between treated and untreated tumors. Results: Five spatial niches were identified, including immune-enriched perivascular regions and infiltrative tumor-immune interfaces. Recurrent tumors showed contraction of adaptive immunity, with downregulation of CD4+ T-helper subsets, Th1, Th2, Th17, and Tfh (log2FC ≈ -3), and depletion of total CD4+ T cells (-2.9). This reduction was greatest in previously treated patients suggesting therapy-associated collapse of adaptive immune niches. Myeloid cells including macrophages and microglia, were preserved or increased, indicating a shift toward myeloid-dominant, immunosuppressive microenvironment. Perivascular immune regions demonstrated reduced T-helper diversity and enhanced myeloid signaling, consistent with immune exclusion and vascular remodeling. These patterns persisted after propensity score matching, with treated recurrences enriched for myeloid-driven immunosuppressive niches (p < 0.05). Applying cNMF-derived activity programs, treated recurrent tumors showed upregulation of systemic inflammatory genes (IL1B, OSMR, CXCL8) but downregulation of microglial inflammatory genes (CXCR4, CX3CR1, JUN, EGR1), reflecting partial loss of lymphocyte related pathways. Complement-associated immunosuppressive programs were mildly increased, while scavenger receptor-associated programs were slightly reduced, indicating therapy-related myeloid shifts. Untreated recurrences had upregulation of inflammatory and immunosuppressive programs, reflecting activated and suppressive immune states. Validation with Xenium and CODEX will be presented. Conclusion: Recurrent tumors undergo remodeling marked by collapse of adaptive immune niches, loss of CD4+ T-helper diversity, and a shift toward myeloid-dominant signaling. Treated recurrences show weaker microglial inflammatory activity and partial transition to a myeloid-driven immunosuppressive state, whereas untreated recurrences display activation of inflammatory and suppressive programs. These findings identify therapy-associated depletion of adaptive immunity and enrichment of suppressive myeloid niches, a features that can be exploited to identify therapeutic targets. Citation Format: Julia Louw, Kenan Zhang, Anna Corcoran, Elizabeth Owens, Jodie Jepson, Jose R. Conejo-Garcia, David M. Ashley, Kanish Mirchia, David R. Raleigh, Mustafa Khasraw. Spatial immune and vascular remodeling defines recurrence in oligodendroglioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6212.