The Controversial Role of Microglia in Malignant Gliomas

Table 2

Molecules/targets in GAMs for therapeutic modulation.

Molecule/agent	Classification	Mechanism	Reference
CSF-1R	Cytokine receptor	Inhibits glioblastoma invasion by targeting glioblastoma-associated microglia via inhibition of the CSF-1R	[16, 111]
TGF𝛽1	Cytokine	GAMs enhance the invasion of GSCs via TGF𝛽1 signaling pathway, which increases the production of MMP-9 by GSCs	[77, 112]
IL-4	Cytokine	Inhibits inflammatory mRNA expression in mixed rat glial and in isolated microglia cultures	[113]
IL-16	Cytokine	Expression correlates with WHO grades of human astrocytic brain tumors	[114]
MCP-1	Cytokine	A positive amplification circuit for macrophage recruitment in gliomas	[115]
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP)	Neuropeptides	Inhibit the production of inflammatory mediators by activated microglia, thus, defined as “microglia-deactivating factors”	[116]
STAT-3	Transcription factor	STAT3 inhibition activates tumor macrophages and abrogates glioma growth	[44, 117–119]
Cyclophosphamide (CPA)	Alkylating agent	Pretreatment with CPA inhibits an increase of CD68^+ and CD163^+ cells and therefore enhances HSV replication and oncolysis	[120]
Dexamethasone	Steroid	Inhibits the filtration of microglia into brain tumors	[121]
ATP	Nucleotide	Promotes an anti-inflammatory state in both hematogenous and resident myeloid cells of the CNS	[122]
Radiochemotherapy	Therapy	Depletes CD68^+ microglia	[123]