Table 2.
Immune modifying factors secreted by GBM CSCs and their proposed mechanisms of immune suppression. References include only those studies showing CSC-specific secretion and/or effects
| Factors Secreted by GBM CSCs | Effects on Immune System | References |
|---|---|---|
| Fibrinogen-like protein 2 (FGL2) | CD103+ dendritic cell differentiation, PD1 expression, immunosuppressive macrophage and MDSC expansion, Treg expansion | 135,136 |
| Galectin-3 | Apoptosis of T cells | 137 |
| Macrophage colony-stimulating factor (CSF1) | Immunosuppressive polarization of macrophages | 138 |
| Macrophage inhibitory cytokine 1 (MIC1) | Inhibition of phagocytosis in macrophages and microglia | 110 |
| Macrophage migration inhibitory factor (MIF) | Recruitment of MDSCs and mast cells, downregulation of NKG2D on natural killer and CD8+ T cells | 139–141 |
| Monocyte chemoattractant protein-1 (MCP1/CCL2) | Microglia recruitment, Treg migration | 102,110,111 |
| Osteopontin | Migration of tumor-supportive macrophages | 142 |
| Periostin | Recruitment of immunosuppressive GAMs | 143 |
| Prostaglandin E2 (PGE2) | Putative regulation of Th17 cell differentiation | 111 |
| Transforming growth factor beta 1 (TGFβ1) | Downregulation of MHCII on myeloid cells, inhibition of mature T cell proliferation and cytotoxic activity, proliferation of Tregs | 144,145 |
| Vascular endothelial growth factor (VEGF) | Inhibition of dendritic cell maturation and function | 146 |
| Versican | Induction of MT1-MMP expression in microglia | 147 |
| WISP1 | Survival of tumor-supportive GAMs | 148 |