Table 2: Molecules/targets in GAMs for therapeutic modulation.

Molecule/agentClassificationMechanismReference

CSF-1RCytokine receptorInhibits glioblastoma invasion by targeting glioblastoma-associated microglia via inhibition of the CSF-1R[16, 111]
TGF 1CytokineGAMs enhance the invasion of GSCs via TGF 1 signaling pathway, which increases the production of MMP-9 by GSCs[77, 112]
IL-4CytokineInhibits inflammatory mRNA expression in mixed rat glial and in isolated microglia cultures[113]
IL-16CytokineExpression correlates with WHO grades of human astrocytic brain tumors[114]
MCP-1CytokineA positive amplification circuit for macrophage recruitment in gliomas[115]
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP)NeuropeptidesInhibit the production of inflammatory mediators by activated microglia, thus, defined as “microglia-deactivating factors”[116]
STAT-3Transcription factorSTAT3 inhibition activates tumor macrophages and abrogates glioma growth[44, 117119]
Cyclophosphamide (CPA)Alkylating agentPretreatment with CPA inhibits an increase of CD68+ and CD163+ cells and therefore enhances HSV replication and oncolysis[120]
DexamethasoneSteroidInhibits the filtration of microglia into brain tumors[121]
ATPNucleotidePromotes an anti-inflammatory state in both hematogenous and resident myeloid cells of the CNS[122]
RadiochemotherapyTherapyDepletes CD68+ microglia[123]