Table 1.
Key examples of immune-modulatory mechanisms shared between malignant gliomas and non-CNS tumors.
| Malignant gliomas | Non-CNS tumor | |
|---|---|---|
| TUMOR ANTIGEN PRESENTATION | ||
| Antigen-presenting cells | Glioma-associated microglia and/or macrophages (2–4); DCs (5); B lymphocytes (6); possibly pericytes (7) | DCs (8–11); tumor-associated macrophages (12–14); B lymphocytes (6); possibly pericytes (7) |
| Location of antigen presentation | Brain parenchyma and/or tumor mass (2–4); tumor-draining lymph nodes (15–17) | Tumor-draining lymph nodes (18–20); tumor mass (21) |
| Routes of antigen egress from tumor | Fluid drainage (22, 23); migrating DCs less likely (24–27) | Migrating DCs (28–30) and/or fluid drainage (31) |
| IMMUNOSUPPRESSIVE CYTOKINES | ||
| IL-10 | ||
| Sources | Glioma-associated macrophages and microglia (32) | Tumor cells (33, 34) and/or tumor-associated macrophages (35) |
| Actions | Immunosuppression (various) (36, 37); context-dependent pro-inflammatory and anti-tumor actions (38, 39) | Immunosuppression (various) (40); anti-angiogenesis (41), anti-metastatic (41), anti-tumor (42–44); anti-inflammatory (45) |
| TGF-β | ||
| Sources | Glioma cells (46–48) and glioma-associated immune cells (49) | Tumor cells and tumor-associated immune cells (49–51) |
| Actions | Immunosuppression (various) (52); angiogenesis (53); maintains glioma stem cell populations (54); glioma cell autocrine proliferation (55); pro-invasion (56) | Immunosuppression (various) (50, 57, 58); tumor suppression (50, 57–59) |
| INDOLAMINE 2,3-DIOXYGENASE (IDO) | ||
| Sources | Glioma cells and tumor-associated immune cells (60–62) | Tumor cells, tumor-associated immune cells, and endothelial cells (62–65) |
| Actions | Immunosuppression (various) (66); expansion of Treg population (67, 68) | Immunosuppression (various) (66); expansion of Treg population (67, 68) |
| REGULATORY T LYMPHOCYTES | ||
| Predominant Treg type | nTreg (69) more than iTreg | nTreg more than iTreg (70) |
| Relevant Treg recruitment factors | CCL22 (71–73), CCL2 (71, 74, 75) | CCL2, CCL22 (76–81), CCL17 (81); CCL3, CCL4 (82); CCL5 (83) |
| TUMOR-ASSOCIATED MYELOID CELLS | ||
| Types | Microglia (84, 85), macrophages (86), MDSCs (87) | Macrophages (88), MDSCs (89, 90) |
| Actions | Immunosuppression (various) (91–95); tumor invasion (96); tumor proliferation (97, 98) | Immunosuppression (various) (99); tumor invasion (100); tumor proliferation (100) |
| PD-1/PD-L1 IMMUNE CHECKPOINT | ||
| Sources | Glioma cells (101); microglia (102); glioma-associated macrophages (103); neurons in tumor-adjacent brain tissue (104) | Tumor cells (105–109), tumor-associated macrophages (100, 110, 111); healthy tissue (112–114) |
| Relevant signaling pathways | PI3K/mTOR (101) | PI3K/mTOR (106, 108, 115, 116), MyD88/TRAF6 (117), MEK/ERK (117) |
| Actions | Immunosuppression, esp. via T cell suppression (118, 119); induction of glioma cell death (104) | Immunosuppression, esp. via T cell suppression (120, 121) |