TMIC-59. GLIOBLASTOMA INDUCES THE DIFFERENTIATION AND RECRUITMENT OF NON-CANONICAL ANTI-TUMORAL NEUTROPHILS FROM SKULL BONE MARROW

Abstract The effects of tumor-associated neutrophils (TANs) on glioblastoma biology remain poorly understood. Flow cytometric analysis 5 newly diagnosed fresh tissue specimens surprisingly revealed a high fraction (21.0-34.1%) TANs expressed MHCII, marker antigen-presenting cells not classically associated with and in matched peripheral blood (PBNs). Transcriptomic profiling confirmed that patient upregulated expression MHCII subunits (HLA-DR), chaperones (HLA-DM), costimulatory ligands (CD86/83). Ex vivo cocultures further demonstrated activated patient-matched naïve T an MHCII-dependent manner, while PBNs did (CD25 MFI fold-change: 1.1 vs 3.2, p< 0.001). antitumoral relevance this property was syngeneic mouse glioma model, wherein αLy6G-mediated neutrophil depletion T-cell-competent mice (Balb/c, n= 13) yielded endpoint tumors had reduced CD8+ cell infiltration (p= 0.0024) were 2.4-fold larger by BLI 0.0383) than controls, but no bearing tumor burden T-cell-deficient (athymic) mice. Given the absence MHCII+ circulation, we interrogated inducibility phenotype tumor-conditioned media murine marrow/blood, finding only immature Ly6Glow bone marrow sufficient plasticity to express process foreign antigen as measured DQ-ovalbumin uptake/proteolysis. Because non-inducibility PBNs, investigated hypothesis recruited microenvironment from adjacent skull labeling space CFMDA tumor-implanted mice; at 72h, marrow-derived contributed disproportionately compared all (41.7% 9.3%). As confirmation, first-ever scRNA-seq human TANs, via pseudotime represent developmental lineage seen PBNs. immunostimulatory population, mechanisms promote egress may have therapeutic value.