Table 1.
Overview of included preclinical studies
| Author | Tumor type | Model | Treatment (dosage) | Duration | Group size | Outcome(s) |
|---|---|---|---|---|---|---|
| Cellular studies | ||||||
| Curran et al26 | Glioblastoma | Cells | Dexamethasone (0.01–0.1 µM) | 24 h | N/A | = basal GM-CSF secretion |
| ↓ TNF-α-induced GM-CSF secretion | ||||||
| Gottschall et al27 | Glioblastoma | Cells | Dexamethasone (0.01–0.1 µM) | 6 or 15 h | N/A | ↓ IL-1β-induced IL-6 secretion |
| Herting et al28 | Glioblastoma | Co-cultured macrophages and tumor slices | Dexamethasone (5 µM) | 26 h | N/A | ↓ IL-1α and IL-1β expression by macrophages and microglia |
| Hong et al29 | Glioblastoma | Co-cultured macrophages and tumor cells | Dexamethasone (1–10 µM) | 24 h | N/A | ↓ CXCL8 expression by tumor cells |
| Mukaida et al30 | Glioblastoma | Cells | Dexamethasone (0.00001–1 µM) | 3 or 24 h | N/A | ↓ IL-1α-induced CXCL8 expression and secretion |
| Ott et al31 | Glioblastoma | Cells | Dexamethasone (0.1 µM) | 120 h | N/A | ↓ TDO expression |
| Rieger et al32 | Glioma | Cells | Dexamethasone (0.1 µM) | 24 h | N/A | ↓ LPS- and cytokine-induced nitrite secretion |
| Shinoda et al33 | Glioma | Cells | Dexamethasone (0.002–2 µM) | 6–72 h | N/A | ↓ LPS-induced nitrite secretion |
| ↓ LPS-induced iNOS expression | ||||||
| Wielgat et al34 | Glioma | Co-cultured microglia and tumor cells | Dexamethasone (10 µM) | 24 h | N/A | ↓ IL-1β production by microglia |
| ↑ IL-10 production by microglia | ||||||
| Wielgat et al35 | Glioblastoma | Co-cultured microglia or monocytes and tumor cells | Dexamethasone (10 µM) | 24 h | N/A | ↓ IL-1β, IL-6, IL-8, IL-12, and TNF-α production by microglia and monocytes |
| ↑ IL-10 production by microglia | ||||||
| = IL-10 production by monocytes | ||||||
| Animal studies | ||||||
| Badie et al36 | Glioma | Rats | Dexamethasone (0.1 or 1 mg/kg/day i.p.) | 7 days | 7–10 | ↓ microglia in tumor |
| = macrophages in tumor | ||||||
| ↓ total lymphocytes and T cells in tumor | ||||||
| Giles et al37 | Glioma | Mice | Dexamethasone (0.5–2.5 mg/kg/day p.o.) | 1 h and ≥17 days | 8–10 | = CD4+ T cells, CD8+ T cells, and Tregs in tumor |
| ↓ CD4+ T cells, CD8+ T cells, and Tregs in tumor-draining lymph nodes | ||||||
| ↑ CTLA-4 expression by CD4 + and CD8+ T cells in blood | ||||||
| = or ↑ survival after anti-CTLA-4 | ||||||
| = CD4+ T cells, CD8+ T cells, and Tregs in tumor after anti-CTLA-4 | ||||||
| ↓ CD4+ T cells, CD8+ T cells, and Tregs in tumor-draining lymph nodes after anti-CTLA-4 | ||||||
| Herting et al28 | Glioblastoma | Mice | Dexamethasone (10 mg/kg/day i.p.) | 5 days | 9–15 | ↓ IL-1α and IL-1β expression in tumor |
| ↓ total myeloid cells and macrophages in tumor | ||||||
| = microglia in tumor | ||||||
| ↑ monocytes in blood | ||||||
| = neutrophils in blood | ||||||
| ↓ total lymphocytes in tumor and blood | ||||||
| Iorgulescu et al38 | Glioma | Mice | Dexamethasone (1–10 mg/kg/day i.p.) | 11–22 days | 4–42 | = total myeloid cells, microglia, macrophages, monocytes, DCs, and CD8 + T cells in tumor |
| ↓ T cells, CD4+ T cells, and NK cells in tumor | ||||||
| ↓ total myeloid cells, macrophages, T cells, CD4+ T cells, CD8+ T cells, and NK cells in tumor-draining lymph nodes | ||||||
| = monocytes and DCs in tumor-draining lymph nodes | ||||||
| ↓ total myeloid cells, macrophages, monocytes, DCs, T cells, CD4+ T cells, CD8+ T cells, and NK cells in spleen | ||||||
| ↓ T cells, CD4+ T cells, and CD8+ T cells in thymus ↑ tumor growth after anti-PD-1 |
||||||
| ↓ or = survival after anti-PD-1 | ||||||
| ↓ total myeloid cells, macrophages, monocytes, DCs, CD4+ T cells, and NK cells in tumor after anti-PD-1 | ||||||
| = microglia, T cells, and CD8+ T cells in tumor after anti-PD-1 | ||||||
| ↓ total myeloid cells, macrophages, monocytes, DCs, T cells, CD4+ T cells, CD8+ T cells, and NK cells in tumor-draining lymph nodes after anti-PD-1 | ||||||
| ↓ total myeloid cells, macrophages, monocytes, DCs, T cells, CD4+ T cells, CD8+ T cells, and NK cells in spleen after anti-PD-1 | ||||||
| ↓ T cells, CD4+ T cells, and CD8+ T cells in thymus after anti-PD-1 | ||||||
| Maxwell et al39 | Glioma | Mice | Dexamethasone (10 mg/kg/day i.p.) | 5–28 days | 10 | ↓ CD4+ and CD8+ T cells in tumor-draining lymph nodes |
| ↓ CD4+ T cells, CD8+ T cells, and Tregs in blood | ||||||
| = survival after anti-PD-1 | ||||||
| = CD4+ and CD8+ T cells in tumor-draining lymph nodes after anti-PD-1 | ||||||
| ↓ CD4+ T cells, CD8+ T cells, and Tregs in blood after anti-PD-1 | ||||||
| Ott et al31 | Glioblastoma | Mice | Dexamethasone (1 mg/kg/day i.p.) | 3 days | 2 | ↓ TDO expression in tumor |
| Human studies | ||||||
| Adhikaree et al40 | Glioblastoma | Patients | Dexamethasone (0.5–5 mg/day N/A) | N/A | 5–11 | ↓ CDc1+, CD141+, CD303+, and Slan+ DCs in blood |
| Chitadze et al41 | Glioblastoma | Patients | Dexamethasone (N/A) | N/A | 13–22 | ↑ monocytes and neutrophils in blood |
| ↓ total lymphocytes, CD4+ T cells, CD8+ T cells, and Tregs in blood | ||||||
| = B cells and NK cells in blood | ||||||
| Fries et al42 | Glioblastoma | Patients | Dexamethasone (3–12 mg/day p.o.) | N/A | 6–7 | = IL-1β secretion by monocytes |
| Gustafson et al43 | Glioblastoma | Patients | Dexamethasone (N/A) | N/A | 5–14 | = monocytes in blood |
| ↑ neutrophils in blood | ||||||
| ↓ total lymphocytes, T cells, CD4+ T cells, and Tregs in blood | ||||||
| = CD8+ T cells, B cells, and NK cells in blood | ||||||
| Moyes et al44 | Glioblastoma | Patients | Dexamethasone (N/A) | N/A | 8–17 | ↓ CCL21, CCL22, and CXCL10 in blood |
| ↑ CCL23 in blood | ||||||
| = CCL2, CCL27, and CXCL12 in blood | ||||||
| Otvos et al45 | Glioblastoma | Patients | Dexamethasone (N/A) | N/A | 34–61 | ↓ total lymphocytes in blood |
| = monocytes in blood | ||||||
| Quillien et al46 | Glioblastoma | Patients | Corticosteroids (N/A) | N/A | 18–43 | ↑ neutrophils in blood |
CD, cluster of differentiation; CTLA-4, cytotoxic T lymphocyte antigen 4; DC, dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; N/A, not available or not applicable; NK cell, natural killer cell; PD-1, programmed cell death protein 1; Slan, 6-sulfo LacNAc; TDO, tryptophan 2,3-dioxygenase; TNF, tumor necrosis factor; Treg, regulatory T cell.