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Table 1. Summary of molecular targets for myeloid interactions with glioblastoma (GBM) Table summarizing receptors and
ligands on microglia, macrophages, and glioma cells that are present in the context of GBM tumor microenvironment, along
with their interactions with each other in preclinical and clinical investigations

Molecular targets involved with tumor progression Normal function Aberrant function in Preclinical studies
in GBM tumors
Chemokine (C-X-C motif) Chemokine (C-X-C motif) Chemoattractant for Angiogenesis Brandenburg 2015 [97] - CXCL2 was
ligand 2 (CXCL2)- from receptor 2 (CXCR2)- on neutrophils upregulated and stronger than VEGF in
microglia, macrophages, endothelial cells vitro -blocking CXCL2-CXCR2 resulted
gliomas in diminished glioma sizes - in vivo
deletion of microglia and macrophages
decreased vessel density by 50%
CX3CL1- from neurons CX3CR1- on microglia and Chemokine Deletion on macrophages Feng 2015 [79] - Deletion of Cx3cr1 from
macrophages mediation of promotes gliomagenesis; microglia and macrophages leads to
immune response accumulation of increased tumor incidence and shorter
inflammatory myocytes survival times
Chemokine (C-C motif) Chemokine (C-C motif) Chemoattractant for Recruitment of microglia Carvalho da Fonseca [62] , Zhang
ligand 2 (CCL2)- from receptor 2 (CCR2)- on microglia to tumor site; IL-6 2012 [80] - CCL2 was found to be
microglia and GBM microglia positive feedback cycle produced by GBM - in vitro glioma
for inflammation lines displayed increased invasion of
extracellular collagen matrices when
co-cultured with CCR2 expressing
microglia
CXCL12, from TME CXCR4- on microglia Proinflammatory Vasculogenesis in Tabouret 2015 [98] - CXCR4 blockade in
chemokine signaling radiation-resistant GBM implants lead to decreased VEGf
gliomas and Hif1a expression
HiF1α- from microglia + Angiogenesis Angiogenesis Tabouret 2015 [98] , Brandenberg
GBM 2015 [97] - Decreased Hif1a expression
lead to less angiogenesis and smaller
tumor size
VEGF- from microglia, VEGFR-2/3- on endothelial Angiogenesis Angiogenesis Tabouret 2015 [98] , Brandenberg
macrophages cells 2015 [97] - Decreased VEGF expression
lead to less angiogenesis and smaller
tumor size
CpG DNA Toll-like receptor 9 (TLR9) on Innate Immune Gliomagenesis Carpentier 2010 [67] - Phase II clinical
microglia and macrophages Response trial investigating CpG as a therapeutic
did not find a significant improvement
in progression-free survival, though
a few long-term survivors suggest
potential benefit
CXCL8/IL8 from GBM, CXCR1, CXCR2, on Neutrophil Gliomagenesis, Waugh 2008 [73] , Brandenburg
microglia, macrophages endothelial cells, chemotaxis, chemoresistance, 2015 [97] - Blocking CXCR2 resulted in
macrophages, and microglia angiogenesis invasion, angiogenesis considerably diminished glioma sizes
Membrane type 1 Pro-MMP2 to MMP2 Extracellular matrix Invasion Markovic 2011 [83] - Oral minocycline
metalloprotease (MT1- breakdown administration greatly reduced glioma
MMP) growth in orthotopically implanted
mice - MT1-MMP was decreased in
treated mice and highly upregulated in
untreated mice
Colony stimulating factor 1 Colony stimulating factor Production, Gliomagenesis and Pyonteck 2013 [76] - The brain-
(CSF1) 1 receptor (CSF1R) - on differentiation, immunosuppression penetrant CSF1R inhibitor BLZ945
macrophages and microglia and function of resulted in increased expression
macrophages and of anti-tumor responses in glioma
microglia associated macrophages and resulted
in decreased intracranial growth of
patient-derived glioma xenografts
in mice Yan 2017 [77] - Combination
therapy with CSF1R inhibitor PLX3397
and tyrosine kinase inhibitors dovitinib
and vatalanib resulted in increased
survival in mice glioma models

VEGF: vascular endothelial growth factor