TMIC-77. SINGLE-CELL CHARACTERIZATION OF HUMAN GBM REVEALS REGIONAL DIFFERENCES IN TUMOR-INFILTRATING LEUKOCYTE ACTIVATION

Abstract Clinical trials of systemic T cell checkpoint blockade in GBM patients showed only disappointing results. This may be attributed part to the immunosuppressive components immune tumor microenvironment (iTME). Therefore, major efforts have been undertaken describe iTME on a single level. However, human data composition different regions (contrast enhancing center versus peripheral infiltration zone) remain scarce. Here, we performed high-depth single-cell RNA sequencing (scRNAseq) patient-matched biopsies from and zone five primary patients. Additionally, blood mononuclear cells (PBMC) same were included scRNAseq analysis explore transcriptional changes occurring during circulating cells. Through > 45’000 cells, revealed distinct regional profile microglia (MG) monocyte-derived macrophages (MdM), non-reactive/exhausted MG subcluster an impaired interferon-response signature cytotoxic compartment. Comparing CD8+ T-cells periphery PBMC-derived patient CX3CR1+ T-cell population with effector memory phenotype which is enriched PBMC but lacking periphery. Peripheral mainly composed tissue-resident exhausted functions. Our provides large-scale dissection GBM-associated types complemented by PBMCs, serving as high dimensional reference map iTME.