TMIC-85. MICROGLIA REPLACEMENT CHANGES THE TRANSCRIPTIONAL PROFILE OF TUMOR ASSOCIATED MYELOID CELLS IN MURINE MODELS OF BRAIN MALIGNANCIES

Abstract Tumor associated microglia and macrophages (TAMs) represent a main cell type of brain malignancies demonstrate complex interactions with cancerous cells the tumor microenvironment. These have important implications for progression treatment malignant central nervous system (CNS) tumors. In non-oncological context, it has been shown that endogenous can be replaced by peripheral hematopoietic genetic or pharmacological intervention. A highly efficient replacement protocol (Shibuya et al, Sci Transl Med 2022, PMID:35294256) utilizing myeloablative bone marrow transplantation (BMT) followed microglial depletion via inhibition Colony-stimulating factor-1 receptor (CSF-1R) leads to almost complete repopulation CNS myeloid niche circulation-derived (CDMCs). We investigated if this approach could utilized integrate CDMCs into tumors study changes in TAM signature. Microglia immune-competent mice was intracranial syngeneic lines either high-grade glioma (GL261) breast cancer metastasis (E0771). Lineage tracing proved high intra- peri-tumoral chimerism BMT-graft derived among both models two weeks after injection. (TA-CDMCs) showed similarly activated morphology as naïve TAMs. used single RNA sequencing CD45-positive further profile transcriptomic identity TA-CDMCs. Pathway enrichment analysis revealed an upregulation immune response pathways TA-CDMCs compared regular TAMs, including overexpression genes relevant regulation T activation, suggesting possible modification immune-environment. Strategies manipulate potential provide understanding pathobiology TAMs build basis novel therapeutic approaches neuro-oncological domain.