The Controversial Role of Microglia in Malignant Gliomas

Table 1

Microglia activating agents.

Molecule/agent	Classification	Mechanism/action	Reference
CpG-ODN	TLR9 ligand	Increases microglia tumor infiltration and enhances the antigen-presenting capacity	[87–89]
poly (I:C)	TLR3 ligand	Unknown soluble factors	[90]
IL-12	Th1 cytokine	Increases tumor infiltration and enhances TRAIL and phagocytosis	[91, 92]
TNF	Th1 cytokine	Enhances glioma cytotoxicity	[93]
IFN-𝛾	Th1 cytokine	Upregulates class II MHC antigen expression	[94]
Cytotoxic T cells	Immune cells	Induce microglia activation and recruitment	[95, 96]
C1q, complement receptor 3 (CR3)	Complement	Mediates elimination of tagged synapses and activates microglia	[97, 98]
T11TS/SLFA-3	Glycopeptide	Induces MHC class II expression and facilitates SLFA3/T11TS-CD2 immune activation	[99, 100]
Ceramide	Sphingolipid	Enhances microglia production/secretion of brain-derived neurotrophic factor (BDNF)	[101]
Ganglioside	Glycosphingolipid	Activates microglia via protein kinase C and NADPH oxidase, which regulate activation of NF-𝜅B	[102]
Adenosine	Nucleoside	Acts via A1 adenosine receptors in microglia	[60]
Triggering receptor expressed on myeloid cells-2 (TREM2)	Innate immune receptor	Increases phagocytosis	[103]
Prothrombin	Blood-clotting protein	Activates microglia via kringle-2 domain	[104]
Propentofylline (PPF)	Methylxanthine	Inhibits microglia migration toward tumor cells and decreases MMP-9 expression	[105]
Minocycline	Antibiotic	Reduces glioma expansion and invasion by attenuating microglia MT1-MMP expression	[106]
Cyclosporin (CsA)	Immunosuppressant	Inhibits immunosuppressive microglia via MAPK signaling	[107]
Mifamurtide	Muramyl dipeptide	Enhances macrophage cytotoxicity and has been used for osteosarcoma treatment	[108]
Butyrate	Fatty acid	Anti-inflammatory in primary, brain-derived microglia cells, but is proinflammatory in transformed, proliferating N9 microglia	[109]
I-125	Radioactive isotope	Stimulates microglia/macrophage to remove necrotic debris	[110]