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Figure 1. The immune-suppressive brain tumor microenvironment. Tissue-specific resident-cells, including astrocytes, microglia, oligodendrocytes, and neurons form the tumor microenvironment along with infiltrating immune cells. In brain cancers, the blood-brain barrier, formed of a tight junction of pericytes, endothelial cells, astrocyte end feet, and basement membrane, can become leaky. This allows the recruitment and entry of tumor-infiltrating lymphocytes and MDMs. Within the tumor bed, neurons, tumor-associated macrophages, effector T-cells and tumor cells secrete or express various immunoregulatory factors, as illustrated in Figure 1. This leads to the formation of the immunosuppressive microenvironment characteristic of primary brain tumors, thereby promoting tumor proliferation and immune evasion. This figure contains images from Servier Medical Art. MDM: monocyte-derived macrophages; CCL-2: C-C motif chemokine ligand 2; CD: cluster of differentiation; CSF-1: colony stimulating factor 1; CSF-1R: colony stimulating factor 1 receptor; CTL: cytotoxic T lymphocyte; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; CXCR4: CXC-chemokine receptor 4; FASL: FAS ligand; FGL2: fibrinogen-like protein 2; FLT3: FMS-like tyrosine kinase 3; HLA: human leukocyte antigen; IDO: indoleamine 2,3-dioxygenase; IL: interleukin; LAG3: lymphocyte activation gene 3 protein; NLGN3: neuroligin-3; PD-1: programmed cell death 1; PD-L1: programmed death-ligand 1; PG-E: Prostaglandin-E; STAT3: signal transducer and activator of transcription 3; TGF-β: transforming growth factor β; TIM3: T-cell immunoglobulin mucin receptor 3; Treg: regulatory T-cell; VEGF: vascular endothelial growth factor