Abstract
In this chapter we describe the state of the art knowledge of the role played by myeloid cells in promoting and supporting the growth and the invasive properties of a deadly brain tumor, glioblastoma. We provide a review of the works describing the intercellular communication among glioma and associated microglia/macrophage cells (GAMs) using in vitro cellular models derived from mice, rats and human patients and in vivo animal models using syngeneic or xenogeneic experimental systems. Special emphasis will be given to 1) the timing alteration of brain microenvironment under the influence of glioma, 2) the bidirectional communication among tumor and GAMs, 3) possible approaches to interfere with or to guide these interactions, with the aim to identify molecular and cellular targets which could revert or delay the vicious cycle that favors tumor biology.
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Abbreviations
- ADAM:
-
a disintegrin and metalloproteinase, arg-1, arginase-1
- ATP:
-
adenosine triphosphate
- BDNF:
-
brain-derived neurotrophic factor
- BM:
-
bone marrow
- cAMP:
-
cyclic adenosine monophosphate
- cGMP:
-
cyclic guanosine monophosphate
- CNS:
-
central nervous system
- Cox-2:
-
cyclooxygenase-2
- CSF-1:
-
colony stimulating factor-1
- CXCL:
-
chemokine C-X-C ligand
- ECM:
-
extracellular matrix
- EE:
-
enriched environment
- EGF:
-
epidermal growth factor
- Evs:
-
extracellular vesicles
- FAK:
-
focal adhesion kinase
- FcGR:
-
fragment crystallizable Fc-gamma receptor
- FGL2:
-
fibrinogen-like protein 2
- GAMs:
-
glioma associated microglia/macrophage cells
- GAS6:
-
growth arrest specific 6
- GBM:
-
glioblastoma multiforme
- GDNF:
-
glial-derived neurotrophic factor
- GM-CSF:
-
granulocyte/macrophage colony-stimulating factor
- GPNMB:
-
glycoprotein non-metastatic melanoma protein B
- HGF/SF:
-
hepatocyte growth factor/scatter factor
- HMGB:
-
high-mobility group box
- IFN-γ:
-
interferon-γ
- IL:
-
interleukin
- Irf:
-
interferon regulatory factor
- KCa:
-
Ca2+-activated K channel
- MAPK:
-
mitogen-activated protein kinase
- MFG-E8:
-
milk fat globule EGF like factor 8
- MHC:
-
major histocompatibility complex
- MMP:
-
matrix metalloproteinase
- MS:
-
multiple sclerosis
- NG2/CSPG4:
-
neuron-glial antigen 2/chondroitin sulfate proteoglycan 4
- NK cells:
-
natural killer cells
- NO:
-
nitric oxide
- PD-1:
-
programmed cell death protein-1
- PDGF:
-
platelet derived growth factor
- PKA:
-
protein kinase A
- PKG:
-
protein kinase G
- ProS:
-
protein S
- ROS:
-
reactive oxygen species
- RUNX1:
-
Runt-related transcription factor 1
- SIRPα:
-
signal regulatory protein α
- STAT-2 :
-
signal transducer and activator of transcription 2
- STI1:
-
stress inducible protein 1
- TGF:
-
transforming growth factor
- Tgm2:
-
transglutaminase 2
- TK:
-
thymidine kinase
- TLR:
-
Toll-like receptor
- TRAM-34:
-
1-[(2-Chlorophenyl)diphenyl-methyl]-1H-pyrazole
- TrkB:
-
tropomyosin receptor kinase B
- VEGF:
-
vascular endothelial growth factor
References
Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10(12):1538–1543. https://doi.org/10.1038/nn2014
Akiyama H, McGeer PL (1990) Brain microglia constitutively express beta-2 integrins. J Neuroimmunol 30(1):81–93. PubMed
Alboni S, Poggini S, Garofalo S, Milior G, El Hajj H, Lecours C, Girard I, Gagnon S, Boisjoly-Villeneuve S, Brunello N, Wolfer DP, Limatola C, Tremblay ME, Maggi L, Branchi I (2016) Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment. Brain Behav Immun 58:261–271. https://doi.org/10.1016/j.bbi.2016.07.155
Alliot F, Lecain E, Grima B, Pessac B (1991) Microglial progenitors with a high proliferative potential in the embryonic and adult mouse brain. Proc Natl Acad Sci U S A 88(4):1541–1545. https://doi.org/10.1073/pnas.88.4.1541
Alliot F, Godin I, Pessac B (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res. 117(2):145–152. PubMed PMID: 10567732
Annovazzi L, Mellai M, Bovio E, Mazzetti S, Pollo B, Schiffer D (2018) Microglia immunophenoty** in gliomas. Oncol Lett 15(1):998–1006. https://doi.org/10.3892/ol.2017.7386
Badie B, Schartner J, Klaver J, Vorpahl J (1999) In vitro modulation of microglia motility by glioma cells is mediated by hepatocyte growth factor/scatter factor. Neurosurgery 44(5):1077–1082.; discussion 1082-3. https://doi.org/10.1097/00006123-199905000-00075
Bergamin LS, Braganhol E, Zanin RF, Edelweiss MI, Battastini AM (2012) Ectonucleotidases in tumor cells and tumor-associated immune cells: an overview. J Biomed Biotechnol 2012:959848. https://doi.org/10.1155/2012/959848
Bowman RL, Klemm F, Akkari L, Pyonteck SM, Sevenich L, Quail DF, Dhara S, Simpson K, Gardner EE, Iacobuzio-Donahue CA, Brennan CW, Tabar V, Gutin PH, Joyce JA (2016) Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies. Cell Rep 17(9):2445–2459. https://doi.org/10.1016/j.celrep.2016.10.052
Braganhol E, Zanin RF, Bernardi A, Bergamin LS, Cappellari AR, CampesatoLF,Morrone FB, Campos MM, Calixto JB, Edelweiss MI, Wink MR, Sévigny J, Robson SC,Battastini AM (2012) Overexpression of NTPDase2 in gliomas promotes systemicinflammation and pulmonary injury. Purinergic Signal 8(2):235–243. DOI: https://doi.org/10.1007/s11302-011-9276-1
Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koeglsperger T, Dake B, Wu PM, Doykan CE, Fanek Z, Liu L, Chen Z, Rothstein JD, Ransohoff RM, Gygi SP, Antel JP, Weiner HL (2014) Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 17(1):131–143. https://doi.org/10.1038/nn.3599
Cao L, Liu X, Lin EJ, Wang C, Choi EY, Riban V, Lin B, During MJ (2010) Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition. Cell 142:52–64. https://doi.org/10.1016/j.cell.2010.05.029
Casella G, Garzetti L, Gatta AT, Finardi A, Maiorino C, Ruffini F, Martino G, Muzio L, Furlan R (2016) IL4 induces IL6-producing M2 macrophages associated to inhibition of neuroinflammation in vitro and in vivo. J. Neuroinflammation 13(1):139 https://doi.org/10.1186/s12974-016-0596-5
Chabry J, Nicolas S, Cazareth J, Murris E, Guyon A, Glaichenhaus N, Heurteaux C, Petit-Paitel A (2015) Enriched environment decreases microglia and brain macrophages inflammatory phenotypes through adiponectin-dependent mechanisms: relevance to depressive-like behavior. Brain Behav Immun 50:275–287. https://doi.org/10.1016/j.bbi.2015.07.018
Chang GH, Barbaro NM, Pieper RO (2000) Phosphatidylserine-dependent phagocytosis of apoptotic glioma cells by normal human microglia, astrocytes, and glioma cells. Neuro-Oncology 2(3):174–183. https://doi.org/10.1093/neuonc/2.3.174
Chen Z, Feng X, Herting CJ, Garcia VA, Nie K, Pong WW, Rasmussen R, Dwivedi B, Seby S, Wolf SA, Gutmann DH, Hambardzumyan D (2017) Cellular and molecular identity of tumor-associated macrophages in glioblastoma. Cancer Res 77(9):2266–2278. https://doi.org/10.1158/0008-5472.CAN-16-2310
Chen Z, Ross JL, Hambardzumyan D (2019) Intravital 2-photon imaging reveals distinct morphology and infiltrative properties of glioblastoma-associated macrophages. Proc Natl Acad Sci U S A 116(28):14254–14259. https://doi.org/10.1073/pnas.1902366116
Coniglio SJ, Eugenin E, Dobrenis K, Stanley ER, West BL, Symons MH, Segall JE (2012) Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med 18:519–527. https://doi.org/10.2119/molmed.2011.00217
Correale J (2014, Sep 20) The role of microglial activation in disease progression. Mult Scler J 20(10):1288–1295. https://doi.org/10.1177/1352458514533230. Epub 2014 May 8. Review. PubMed PMID: 24812046
D’Alessandro G, Catalano M, Sciaccaluga M, Chece G, Cipriani R, Rosito M, Grimaldi A, Lauro C, Cantore G, Santoro A, Fioretti B, Franciolini F, Wulff H, Limatola C (2013) KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in vivo. Cell Death Dis 4:e773. https://doi.org/10.1038/cddis.2013.279
D’Alessandro G, Grimaldi A, Chece G, Porzia A, Esposito V, Santoro A, Salvati M, Mainiero F, Ragozzino D, Di Angelantonio S, Wulff H, Catalano M, Limatola C (2016). KCa3.1 channel inhibition sensitizes malignant gliomas to temozolomide treatment. Oncotarget. 7(21):30781–30796. https://doi.org/10.18632/oncotarget.8761
D’Alessandro G, Monaco L, Catacuzzeno L, Antonangeli F, Santoro A, Esposito V, Franciolini F, Wulff H, Limatola C (2019) Radiation increases functional KCa3.1 expression and invasiveness in glioblastoma. Cancers (Basel) 11(3):pii: E279. https://doi.org/10.3390/cancers11030279
Dijksterhuis JP, Arthofer E, Marinescu VD, Nelander S, Uhlén M, Pontén F, Mulder J, Schulte G (2015) High levels of WNT-5A in human glioma correlate with increased presence of tumor-associated microglia/monocytes. Exp Cell Res 339(2):280–288. https://doi.org/10.1016/j.yexcr.2015.10.022
Dzaye O, Hu F, Derkow K, Haage V, Euskirchen P, Harms C, Lehnardt S, SynowitzM WSA, Kettenmann H (2016) Glioma stem cells but not bulk glioma cells upregulate IL-6 secretion in microglia/brain macrophages via toll-like receptor 4 signaling. J Neuropathol Exp Neurol 75(5):429–440. https://doi.org/10.1093/jnen/nlw016
Dziurzynski K, Wei J, Qiao W, Hatiboglu MA, Kong LY, Wu A, Wang Y, Cahill D, Levine N, Prabhu S, Rao G, Sawaya R, Heimberger AB (2011) Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin Cancer Res 17(14):4642–4649. https://doi.org/10.1158/1078-0432.CCR-11-0414
Ebert S, Gerber J, Bader S, Mühlhauser F, Brechtel K, Mitchell TJ, Nau R (2005) Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination. J Neuroimmunol 159(1–2):87–96. https://doi.org/10.1016/j.jneuroim.2004.10.005
Eder C, Klee R, Heinemann U (1997) Pharmacological properties of Ca2+−activated K+ currents of ramified murine brain macrophages. NaunynSchmiedebergs Arch Pharmacol 356(2):233–239. PMID: 9272730
Ehninger D, Kempermann G (2003) Regional effects of wheel running and environmental enrichment on cell genesis and microglia proliferation in the adult murine neocortex. Cereb Cortex 13:845–851. https://doi.org/10.1093/cercor/13.8.845
Ehninger D, Wang LP, Klempin F, Römer B, Kettenmann H, Kempermann G (2011) Enriched environment and physical activity reduce microglia and influence the fate of NG2 cells in the amygdala of adult mice. Cell Tissue Res 345:69–86. https://doi.org/10.1007/s00441-011-1200-z
El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13(4):432–438. https://doi.org/10.1038/nm1555
Ellert-Miklaszewska A, Dabrowski M, Lipko M, Sliwa M, Maleszewska M, Kaminska B (2013) Molecular definition of the pro-tumorigenic phenotype of glioma-activated microglia. Glia 61(7):1178–1190. https://doi.org/10.1002/glia.22510
Ellert-Miklaszewska A, Wisniewski P, Kijewska M, Gajdanowicz P, PszczolkowskaD PP, Dabrowski M, Maleszewska M, Kaminska B (2016) Tumour-processed osteopontin and lactadherin drive the protumorigenic reprogramming of microglia and glioma progression. Oncogene 35(50):6366–6377. https://doi.org/10.1038/onc.2016.55
El-Obeid A, Bongcam-Rudloff E, Sörby M, Ostman A, Nistér M, Westermark B (1997) Cell scattering and migration induced by autocrine transforming growth factor alpha inhuman glioma cells in vitro. Cancer Res 57(24):5598–55604. PMID: 9407973
Färber K, Synowitz M, Zahn G, Vossmeyer D, Stragies R, van Rooijen N, Kettenmann H (2008) An alpha5beta1 integrin inhibitor attenuates glioma growth. Mol Cell Neurosci 39(4):579–585. https://doi.org/10.1016/j.mcn.2008.08.005
Fedoroff S, Zhai R, Novak JP (1997) Microglia and astroglia have a common progenitor cell. J Neurosci Res 50(3):477–486. https://doi.org/10.1002/(SICI)1097-4547(19971101)50:3<477::AID-JNR14>3.0.CO;2-3
Feng X, Szulzewsky F, Yerevanian A, Chen Z, Heinzmann D, Rasmussen RD, Alvarez-Garcia V, Kim Y, Wang B, Tamagno I, Zhou H, Li X, Kettenmann H, Ransohoff RM, Hambardzumyan D (2015) Loss of CX3CR1 increases accumulation of inflammatorymonocytes and promotes gliomagenesis. Oncotarget 6(17):15077–15094. https://doi.org/10.18632/oncotarget.3730
Ferreira R, Lively S, Schlichter LC (2014) IL-4 type 1 receptor signaling up-regulates KCNN4 expression, and increases the KCa3.1 current and its contribution to migration of alternative-activated microglia. Front Cell Neurosci 8:183. https://doi.org/10.3389/fncel.2014.00183
Ferreira R, Wong R, Schlichter LC (2015) KCa3.1/IK1 channel regulation by cGMP-dependent protein kinase (PKG) via reactive oxygen species and CaMKII in microglia: an immune modulating feedback system?. Front Immunol 6:153. https://doi.org/10.3389/fimmu.2015.00153
Fonseca AC, Romão L, Amaral RF, Assad Kahn S, Lobo D, Martins S, Marcondes de Souza J, Moura-Neto V, Lima FR (2012) Microglial stress inducible protein 1 promotes proliferation and migration in human glioblastoma cells. Neuroscience 200:130–141. https://doi.org/10.1016/j.neuroscience.2011.10.025
Gabrusiewicz K, Ellert-Miklaszewska A, Lipko M, Sielska M, Frankowska M, Kaminska B (2011) Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas. PLoS One 6(8):e23902. https://doi.org/10.1371/journal.pone.0023902
Galarneau H, Villeneuve J, Gowing G, Julien JP, Vallières L (2007) Increased glioma growth in mice depleted of macrophages. Cancer Res 67(18):8874–8881. https://doi.org/10.1158/0008-5472.CAN-07-0177
Garofalo S, D’Alessandro G, Chece G, Brau F, Maggi L, Rosa A, Porzia A, Mainiero F, Esposito V, Lauro C, Benigni G, Bernardini G, Santoni A, Limatola C (2015) Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice. Nat Commun 6:6623. https://doi.org/10.1038/ncomms7623
Garofalo S, Porzia A, Mainiero F, Di Angelantonio S, Cortese B, Basilico B, Pagani F, Cignitti G, Chece G, Maggio R, Tremblay ME, Savage J, Bisht K, Esposito V, Bernardini G, Seyfried T, Mieczkowski J, Stepniak K, Kaminska B, Santoni A, Limatola C (2017) Environmental stimuli shape microglial plasticity in glioma. Elife 6:pii: e33415. https://doi.org/10.7554/eLife.33415
Ghosh A, Mukherjee J, Bhattacharjee M, Sarkar P, Acharya S, Chaudhuri S, Chaudhuri S (2007, May 30) The other side of the coin: beneficiary effect of ‘oxidative burst’ upsurge with T11TS facilitates the elimination of glioma cells. Cell Mol Biol (Noisy-le-grand) 53(5):53–62. PubMed PMID: 17543233
Gieryng A, Pszczolkowska D, Walentynowicz KA, Rajan WD, Kaminska B (2017) Immune microenvironment of gliomas. Lab Investig 97(5):498–518. https://doi.org/10.1038/labinvest.2017.19
Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate map** analysis reveals that adult microglia derive from primitive macrophages. Science 330(6005):841–845. https://doi.org/10.1126/science.1194637
Gjorgjevski M, Hannen R, Carl B, Li Y, Landmann E, Buchholz M, Bartsch JW, Nimsky C (2019) Molecular profiling of the tumor microenvironment in glioblastoma patients: correlation of microglia/macrophage polarization state with metalloprotease expression profiles and survival. . Biosci Rep 39(6):Pii: BSR20182361. https://doi.org/10.1042/BSR20182361
Goldmann T, Wieghofer P, Jordão MJ, Prutek F, Hagemeyer N, Frenzel K, Amann L, Staszewski O, Kierdorf K, Krueger M, Locatelli G, Hochgerner H, Zeiser R, Epelman S, Geissmann F, Priller J, Rossi FM, Bechmann I, Kerschensteiner M, Linnarsson S, Jung S, Prinz M (2016) Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat Immunol 17:797–805. https://doi.org/10.1038/ni.3423
Graeber MB, Scheithauer BW, Kreutzberg GW (2002) Microglia in brain tumors. Glia 40(2):252–259. PubMed
Greter M (2016) Family ties among CNS macrophages. Nat Immunol 17(7):742–743. https://doi.org/10.1038/ni.3490
Grimaldi A, D’Alessandro G, Golia MT, Grössinger EM, Di Angelantonio S, Ragozzino D, Santoro A, Esposito V, Wulff H, Catalano M, Limatola C (2016) KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages. Cell Death Dis7:e2174. https://doi.org/10.1038/cddis.2016.73
Hambardzumyan D, Gutmann DH, Kettenmann H (2016) The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci 19(1):20–27. https://doi.org/10.1038/nn.4185
Hamilton L, Astell KR, Velikova G, Sieger DA (2016) Zebrafish live imaging model reveals differential responses of microglia toward glioblastoma cells in vivo. Zebrafish 6:523–534. https://doi.org/10.1089/zeb.2016.1339
Hammond TR, Marsh SE, Stevens B (2019) Immune Signaling in Neurodegeneration. Immunity 50(4):955–974. https://doi.org/10.1016/j.immuni.2019.03.016
Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10(11):1387–1394. https://doi.org/10.1038/nn1997
Hao C, Richardson A, Fedoroff S (1991) Macrophage-like cells originate from neuroepithelium in culture: characterization and properties of the macrophage-like cells. Int J Dev Neurosci 9(1):1–14. PMID: 2014762
Hardcastle J, Mills L, Malo CS, ** F, Kurokawa C, Geekiyanage H, Schroeder M, Sarkaria J, Johnson AJ, Galanis E (2017) Immunovirotherapy with measles virus strains in combination with anti-PD-1 antibody blockade enhances antitumor activity in glioblastoma treatment. Neuro-Oncology 19(4):493–502. https://doi.org/10.1093/neuonc/now179
Held-Feindt J, Hattermann K, Müerköster SS, Wedderkopp H, Knerlich-LukoschusF UH, Mehdorn HM, Mentlein R (2010) CX3CR1 promotes recruitment of humanglioma-infiltrating microglia/macrophages (GIMs). Exp Cell Res 316(9):1553–1566. https://doi.org/10.1016/j.yexcr.2010.02.018
Henrik Heiland D, Ravi VM, Behringer SP, Frenking JH, Wurm J, Joseph K, Garrelfs NWC, Strähle J, Heynckes S, Grauvogel J, Franco P, Mader I, Schneider M, Potthoff AL, Delev D, Hofmann UG, Fung C, Beck J, Sankowski R, Prinz M, Schnell O (2019) Tumor-associated reactive astrocytes aid the evolution of immunosuppressiveenvironment in glioblastoma. Nat Commun 10(1):2541. https://doi.org/10.1038/s41467-019-10493-6
Hishii M, Nitta T, Ishida H, Ebato M, Kurosu A, Yagita H, Sato K, Okumura K (1995) Human glioma-derived interleukin-10 inhibits antitumor immune responses in vitro. Neurosurgery 37(6):1160–1166.; discussion 1166-7. https://doi.org/10.1227/00006123-199512000-00016
Hortega PDR (1919) El tercerelemento de los centrosnerviosos. Bol Soc Esp d Biol 9:69–120
Hu F, Dzaye O, Hahn A, Yu Y, Scavetta RJ, Dittmar G, Kaczmarek AK, Dunning KR, Ricciardelli C, Rinnenthal JL, Heppner FL, Lehnardt S, Synowitz M, Wolf SA, Kettenmann H (2015) Glioma-derived versican promotes tumor expansion via glioma-associated microglial/macrophages Toll-like receptor 2 signaling. Neuro-Oncology 17(2):200–210. https://doi.org/10.1093/neuonc/nou324
Hutter G, Theruvath J, Graef CM, Zhang M, Schoen MK, Manz EM, Bennett ML, Olson A, Azad TD, Sinha R, Chan C, Assad Kahn S, Gholamin S, Wilson C, Grant G, He J, Weissman IL, Mitra SS, Cheshier SH (2019) Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma. Proc Natl Acad Sci U S A 116(3):997–1006. https://doi.org/10.1073/pnas.1721434116
Jack CS, Arbour N, Manusow J, Montgrain V, Blain M, McCrea E, Shapiro A, Antel JP (2005) TLR signaling tailors innate immune responses in human microglia and astrocytes. J Immunol 175(7):4320–4330. https://doi.org/10.4049/jimmunol.175.7.4320
Jacobs VL, Landry RP, Liu Y, Romero-Sandoval EA, De Leo JA (2012) Propentofylline decreases tumor growth in a rodent model of glioblastoma multiforme by a direct mechanism on microglia. Neuro-Oncology 14(2):119–131. https://doi.org/10.1093/neuonc/nor194
Jaiswal S, Jamieson CH, Pang WW, Park CY, Chao MP, Majeti R, Traver D, van Rooijen N, Weissman IL (2009) CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell 138(2):271–285. https://doi.org/10.1016/j.cell.2009.05.046
Jan HJ, Lee CC, Shih YL, Hueng DY, Ma HI, Lai JH, Wei HW, Lee HM (2010) Osteopontin regulates human glioma cell invasiveness and tumor growth in mice. Neuro Oncol 12:58–70 https://doi.org/10.1093/neuonc/nop013
Juliano J, Gil O, Hawkins-Daarud A, Noticewala S, Rockne RC, Gallaher J,Massey SC, Sims PA, Anderson ARA, Swanson KR, Canoll P (2018) Comparative dynamics of microglial and glioma cell motility at the infiltrative margin of brain tumours. J R Soc Interf 15(139): pii: 20170582. https://doi.org/10.1098/rsif.2017.0582
Kierdorf K, Erny D, Goldmann T, Sander V, Schulz C, Perdiguero EG, Wieghofer P, Heinrich A, Riemke P, Hölscher C, Müller DN, Luckow B, Brocker T, Debowski K, Fritz G, Opdenakker G, Diefenbach A, Biber K, Heikenwalder M, Geissmann F, Rosenbauer F, Prinz M (2013) Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci 16(3):273–280. https://doi.org/10.1038/nn.3318
Kitamura T, Miyake T, Fujita S (1984) Genesis of resting microglia in the gray matter of mouse hippocampus. J Comp Neurol 226(3):421–433. https://doi.org/10.1016/j.cell.2009.05.046
Ku MC, Wolf SA, Respondek D, Matyash V, Pohlmann A, Waiczies S, Waiczies H, Niendorf T, Synowitz M, Glass R, Kettenmann H (2013 Apr) GDNF mediates glioblastoma-inducedmicroglia attraction but not astrogliosis. Acta Neuropathol 125(4):609–620. https://doi.org/10.1016/j.cell.2012.01.024
Lepore F, D’Alessandro G, Antonangeli F, Santoro A, Esposito V, Limatola C, Trettel F (2018) CXCL16/CXCR6 axis drives microglia/macrophages phenotype in physiological conditions and plays a crucial role in glioma. Front Immunol 9:2750. https://doi.org/10.3389/fimmu.2018.02750
Li F, Lv B, Liu Y, Hua T, Han J, Sun C, Xu L, Zhang Z, Feng Z, Cai Y, Zou Y, Ke Y, Jiang X (2017) Blocking the CD47-SIRPα axis by delivery of anti-CD47 antibody induces antitumor effects in glioma and glioma stem cells. Oncoimmunology 7(2):e1391973. PMID: 29308321. https://doi.org/10.1080/2162402X.2017.1391973
Liu C, Luo D, Streit WJ, Harrison JK (2008) CX3CL1 and CX3CR1 in the GL261 murine model of glioma: CX3CR1 deficiency does not impact tumor growth or infiltration of microglia and lymphocytes. J Neuroimmunol 198(1–2):98–105. https://doi.org/10.1016/j.jneuroim.2008.04.016
Lively S, SchlichteR LC (2013) The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion. J. Neuroinflammat 10:75. https://doi.org/10.1186/1742-2094-10-75
Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5(4):331–342. https://doi.org/10.1038/nri1594
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1
Majumdar A, Cruz D, Asamoah N, Buxbaum A, Sohar I, Lobel P, Maxfield FR (2007) Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils. Mol Biol Cell 18(4):1490–1496. https://doi.org/10.1091/mbc.e06-10-0975
Markovic DS, Glass R, Synowitz M, Rooijen NV, Kettenmann H (2005) Microglia stimulate the invasiveness of glioma cells by increasing the activity of metalloprotease-2. J Neuropathol Exp Neurol 64(9):754–762. https://doi.org/10.1097/01.jnen.0000178445.33972.a9
Markovic DS, Vinnakota K, Chirasani S, Synowitz M, Raguet H, Stock K, Sliwa M, Lehmann S, Kälin R, van Rooijen N, Holmbeck K, Heppner FL, Kiwit J, Matyash V, Lehnardt S, Kaminska B, Glass R, Kettenmann H (2009) Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci U S A 106(30):12530–12535. https://doi.org/10.1073/pnas.0804273106
Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime rep. 6:13. DOI: https://doi.org/10.12703/P6-13. eCollection 2014
Masuda T, Tsuda M, Yoshinaga R, Tozaki-Saitoh H, Ozato K, Tamura T, Inoue K (2012) IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Cell Rep 1:334–340. https://doi.org/10.1016/j.celrep.2012.02.014. Epub 2012 Apr 5
Matias D, Dubois LG, Pontes B, Rosário L, Ferrer VP, Balça-Silva J, Fonseca ACC, Macharia LW, Romão LE, TCLS S, Chimelli L, Filho PN, Lopes MC, Abreu JG, FRS L, Moura-Neto V (2019) GBM-derived Wnt3a induces M2-like phenotype in microglial cells through Wnt/β-catenin signaling. Mol Neurobiol 56(2):1517–1530. https://doi.org/10.1007/s12035-018-1150-5. Epub 2018 Jun 14
McKercher SR, Torbett BE, Anderson KL, Henkel GW, Vestal DJ, Baribault H, Klemsz M, Feeney AJ, Wu GE, Paige CJ, Maki RA (1996) Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J 15(20):5647–5658. PMID: 8896458
Murabe Y, Sano Y (1982) Morphological studies on neuroglia. VI Postnatal development of microglial cells. Cell Tissue Res 225(3):469–485. https://doi.org/10.1007/bf00214798
Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, Locati M, Mantovani A, Martinez FO, Mege JL, Mosser DM, Natoli G, Saeij JP, Schultze JL, Shirey KA, Sica A, Suttles J, Udalova I, van Ginderachter JA, Vogel SN, Wynn TA (2014) Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41(1):14–20. https://doi.org/10.1016/j.immuni.2014.06.008
Nachat-Kappes R, Pinel A, Combe K, Lamas B, Farges MC, Rossary A, Goncalves-Mendes N, Caldefie-Chezet F, Vasson MP, Basu S (2012) Effects of enriched environment on COX-2, leptin and eicosanoids in a mouse model of breast cancer. PLoS One 7:e51525. https://doi.org/10.1371/journal.pone.0051525
Neher JJ, Neniskyte U, Brown GC (2012) Primary phagocytosis of neurons by inflamed microglia: potential roles in neurodegeneration. Front Pharmacol 3:27. https://doi.org/10.3389/fphar.2012.00027
Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318. https://doi.org/10.1126/science.1110647
Okada M, Saio M, Kito Y, Ohe N, Yano H, Yoshimura S, Iwama T, Takami T (2009) Tumor-associated macrophage/microglia infiltration in human gliomas is correlated with MCP-3, but not MCP-1. Int J Oncol 34(6):1621–1627. https://doi.org/10.3892/ijo_00000292
Osterberg N, Ferrara N, Vacher J, Gaedicke S, Niedermann G, Weyerbrock A, Doostkam S, Schaefer HE, Plate KH, Machein MR (2016) Decrease of VEGF-A in myeloidcells attenuates glioma progression and prolongs survival in an experimentalglioma model. Neuro-oncology 18(7):939–949. https://doi.org/10.1093/neuonc/now005
Pan Y, **ong M, Chen R, Ma Y, Corman C, Maricos M, Kindler U, Semtner M, Chen YH, Dahiya S, Gutmann DH (2018) Athymic mice reveal a requirement for T-cell-microglia interactions in establishing a microenvironment supportive of Nf1 low-grade glioma growth. Genes Dev 32(7–8):491–496. https://doi.org/10.1101/gad.310797.117
Pellegatti P, Raffaghello L, Bianchi G, Piccardi F, Pistoia V, Di Virgilio F (2008) Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase. PLoS One 3(7):e2599. https://doi.org/10.1371/journal.pone.0002599
Penfield W (1925) Microglia and the process of phagocytosis in gliomas. Am J Pathol 1:77–97. PMID: 19969634
Perry VH, Hume DA, Gordon S (1985) Immunohistochemical localization of macrophages and microglia in the adult and develo** mouse brain. Neuroscience 15(2):313–326. https://doi.org/10.1016/0306-4522(85)90215-5
Poli A, Wang J, Domingues O, Planagumà J, Yan T, Rygh CB, Skaftnesmo KO, Thorsen F, McCormack E, Hentges F, Pedersen PH, Zimmer J, Enger PØ, Chekenya M (2013) Targeting glioblastoma with NK cells and mAb against NG2/CSPG4 prolongs animal survival. Oncotarget 4(9):1527–1546. https://doi.org/10.18632/oncotarget.1291
Priego N, Zhu L, Monteiro C, Mulders M, Wasilewski D, Bindeman W, Doglio L, Martínez L, Martínez-Saez E, Ramón Y, Cajal S, Megías D, Hernández-Encinas E, Blanco-Aparicio C, Martínez L, Zarzuela E, Muñoz J, Fustero-Torre C, Piñeiro-Yáñez E, Hernández-Laín A, Bertero L, Poli V, Sanchez-Martinez M, Menendez JA, Soffietti R, Bosch-Barrera J, Valiente M (2018) STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med 24(7):1024–1035. https://doi.org/10.1038/s41591-018-0044-4
Prinz M, Priller J (2014) Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci 15:300–312. https://doi.org/10.1038/nrn3722
Prionisti I, Bühler LH, Walker PR, Jolivet RB (2019) Harnessing microglia and macrophages for the treatment of glioblastoma. Front Pharmacol 10:506. https://doi.org/10.3389/fphar.2019.00506
Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, Olson OC, Quick ML, Huse JT, Teijeiro V, Setty M, Leslie CS, Oei Y, Pedraza A, Zhang J, Brennan CW, Sutton JC, Holland EC, Daniel D, Joyce JA (2013) CSF-1R inhibition altersmacrophage polarization and blocks glioma progression. Nat Med 19(10):1264–1272. https://doi.org/10.1038/nm.3337
Qian J, Luo F, Yang J, Liu J, Liu R, Wang L, Wang C, Deng Y, Lu Z, Wang Y, Lu M, Wang JY, Chu Y (2018) TLR2 promotes glioma immune evasion by Downregulating MHC class II molecules in microglia. Cancer Immunol Res 6(10):1220–1233. https://doi.org/10.1158/2326-6066.CIR-18-0020
Qin T, Wang C, Chen X, Duan C, Zhang X, Zhang J, Chai H, Tang T, Chen H, Yue J, Li Y, Yang J (2015) Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma. Toxicol Appl Pharmacol 286(2):112–123. https://doi.org/10.1016/j.taap.2015.03.021
Quail DF, Joyce JA (2017) The microenvironmental landscape of brain tumors. Cancer Cell 31(3):326–341. https://doi.org/10.1038/nn.4338
Ransohoff RM (2016) A polarizing question: do M1 and M2 microglia exist? Nat Neurosci 19(8):987–991
Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468:253–262. https://doi.org/10.1038/nature09615
Resende FF, Bai X, Del Bel EA, Kirchhoff F, Scheller A, Titze-de-Almeida R (2016) Evaluation of TgH(CX3CR1-EGFP) mice implanted with mCherry-GL261 cells as an in vivo model for morphometrical analysis of glioma-microglia interaction. BMC Cancer 16:72. https://doi.org/10.1186/s12885-016-2118-3
Ricard C, Tchoghandjian A, Luche H, Grenot P, Figarella-Branger D, Rougon G, Malissen M, Debarbieux F (2016) Phenotypic dynamics of microglial and monocyte-derived cells in glioblastoma-bearing mice. Sci Rep 6:26381. https://doi.org/10.1038/srep26381
Ricciardelli C, Sakko AJ, Ween MP, Russell DL, Horsfall DJ (2009) The biological role and regulation of versican levels in cancer. Cancer Metastasis Rev 28(1–2):233–245. https://doi.org/10.1007/s10555-009-9182-y
Rodero M, Marie Y, Coudert M, Blondet E, Mokhtari K, Rousseau A, Raoul W, Carpentier C, Sennlaub F, Deterre P, Delattre JY, Debré P, Sanson M, Combadière C (2008) Polymorphism in the microglial cell-mobilizing CX3CR1 gene is associated with survival in patients with glioblastoma. J ClinOncol 26(36):5957–5964. https://doi.org/10.1200/JCO.2008.17.2833
Rodrıguez JJ, Noristani HN, Verkhratsky A (2015) Microglial response to Alzheimer’s disease is differentially modulated by voluntary wheel running and enriched environments. Brain Struct Funct 220:941–953. https://doi.org/10.1007/s00429-013-0693-5
Roggendorf W, Strupp S, Paulus W (1996) Distribution and characterization of microglia/macrophages in human brain tumors. Acta Neuropathol 92(3):288–293. PMID: 8870831
Rolón-Reyes K, Kucheryavykh YV, Cubano LA, Inyushin M, Skatchkov SN, Eaton MJ, Harrison JK, Kucheryavykh LY (2015) Microglia activate migration of glioma cells through a Pyk2 intracellular pathway. PLoS One 10(6):e0131059. https://doi.org/10.1371/journal.pone.0131059
Rosenzweig MR, Bennett EL (1996) Psychobiology of plasticity: effects of training and experience on brain and behavior. Behav Brain Res 78:57–65. PMID: 8793038
Rosenzweig MR, Bennett EL, Krech D (1964) Cerebral effects of environmental complexity and training among adult rats. J Comp Physiol Psychol 57:438–439. PMID: 14155385
Sale A, Berardi N, Maffei L (2014) Environment and brain plasticity: towards an endogenous pharmacotherapy. Physiol Rev 94:189–234. https://doi.org/10.1152/physrev.00036.2012
Sarkar S, Döring A, Zemp FJ, Silva C, Lun X, Wang X, Kelly J, Hader W, Hamilton M, Mercier P, Dunn JF, Kinniburgh D, van Rooijen N, Robbins S, Forsyth P, Cairncross G, Weiss S, Yong VW (2014) Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells. Nat Neurosci 17(1):46–55. https://doi.org/10.1038/nn.3597
Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:691–705. https://doi.org/10.1016/j.neuron.2012.03.026
Scheiblich H, Roloff F, Singh V, Stangel M, Stern M, Bicker G (2014) Nitric oxide/cyclic GMP signaling regulates motility of a microglial cell line and primary microglia in vitro. Brain Res 564:9–21. https://doi.org/10.1016/j.brainres.2014.03.048
Schilling T, Repp H, Richter H, Koschinski HU, Dreyer F, Eder C (2002) Lysophospholipids induce membrane hyperpolarization in microglia by activation of IKCa1 Ca(2+)- dependent K(+) channels. Neuroscience 109(4):827–835. https://doi.org/10.1016/s0306-4522(01)00534-6
Schilling T, Stock C, Schwab A, Eder C (2004) Functional importance of Ca2+−activated K+ channels for lysophosphatidic acid induced microglial migration. Eur J Neurosci 19(6):1469–1474. https://doi.org/10.1111/j.1460-9568.2004.03265.x
Sciumè G, Soriani A, Piccoli M, Frati L, Santoni A, Bernardini G (2010) CX3CR1/CX3CL1 axis negatively controls glioma cell invasion and is modulated by transforming growth factor-β1. Neuro-Oncology 12(7):701–710. https://doi.org/10.1093/neuonc/nop076
Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476. https://doi.org/10.1038/ncb1800
Squarzoni P, Oller G, Hoeffel G, Pont-Lezica L, Rostaing P, Low D, Bessis A, Ginhoux F, Garel S (2014) Microglia modulate wiring of the embryonic forebrain. Cell Rep 8(5):1271–1279. https://doi.org/10.1016/j.celrep.2014.07.042
Stegen B, Butz L, Klumpp L, Zips D, Dittmann K, Ruth P, Huber SM (2015) Ca2+-activated IK K+ channel blockade radiosensitizes glioblastoma cells. Mol Cancer Res 13(9):1283–1295. https://doi.org/10.1158/1541-7786.MCR-15-0075
Szulzewsky F, Pelz A, Feng X, Synowitz M, Markovic D, Langmann T, Holtman IR, Wang X, Eggen BJ, Boddeke HW, Hambardzumyan D, Wolf SA, Kettenmann H (2015) Glioma-associated microglia/macrophages display an expression profile differentfrom M1 and M2 polarization and highly express Gpnmb and Spp1. PLoS One 10(2):e0116644. https://doi.org/10.1371/journal.pone.0116644
Szulzewsky F, Arora S, de Witte L, Ulas T, Markovic D, Schultze JL, Holland EC, Synowitz M, Wolf SA, Kettenmann H (2016) Human glioblastoma-associated microglia/monocytes express a distinct RNA profile compared to human control and murine samples. Glia 64(8):1416–1436. https://doi.org/10.1002/glia.23014
Szulzewsky F, Schwendinger N, Güneykaya D, Cimino PJ, Hambardzumyan D, Synowitz M, Holland EC, Kettenmann H (2018) Loss of host-derived osteopontin creates a glioblastoma-promoting microenvironment. Neuro-Oncology 20(3):355–366. https://doi.org/10.1093/neuonc/nox165
Takata K, Takada T, Ito A, Asai M, Tawa M, Saito Y, Ashihara E, Tomimoto H, Kitamura Y, Shimohama S (2012) Microglial amyloid-β1-40 phagocytosis dysfunction is caused by high-mobility group box protein-1: implications for the pathological progression of Alzheimer’s disease. Int J Alzheimers Dis 2012:685739. https://doi.org/10.1155/2012/685739
Taraboletti G, D’Ascenzo S, Giusti I, Marchetti D, Borsotti P, Millimaggi D, Giavazzi R, Pavan A, Dolo V (2006) Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced by acidic pH. Neoplasia 8(2):96–103. https://doi.org/10.1593/neo.05583
Tarassishin L, Suh HS, Lee SC (2011) Interferon regulatory factor 3 plays an anti-inflammatory role in microglia by activating the PI3K/Akt pathway. J Neuroinflammation 8:187. https://doi.org/10.1186/1742-2094-8-187
Toyama K, Wulff H, Chandy KG, Azam P, Raman G, Saito T, Fujiwara Y, Mattson DL, Das S, Melvin JE, Pratt PF, Hatoum OA, Gutterman DD, Harder DR, Miura H (2008) The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans. J Clin Invest 118(9):3025–3037. https://doi.org/10.1172/JCI30836
Turner KL, Honasoge A, Robert SM, McFerrin MM, Sontheimer H (2014) A proinvasive role for the ca(2+) -activated K(+) channel KCa3.1 in malignant glioma. Glia 62(6):971–981. https://doi.org/10.1002/glia.22655
van der Vos KE, Abels ER, Zhang X, Lai C, Carrizosa E, Oakley D, Prabhakar S, Mardini O, Crommentuijn MH, Skog J, Krichevsky AM, Stemmer-Rachamimov A, Mempel TR, El Khoury J, Hickman SE, Breakefield XO (2016) Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophagesin the brain. Neuro-Oncology 18(1):58–69. https://doi.org/10.1093/neuonc/nov244
van Hal PT, Hopstaken-Broos JP, Prins A, Favaloro EJ, Huijbens RJ, Hilvering C, Figdor CG, Hoogsteden HC (1994) Potential indirect anti-inflammatory effects of IL-4. Stimulation of human monocytes, macrophages, and endothelial cells by IL-4 increases aminopeptidase-N activity (CD13; EC 3.4.11.2). J Immunol 153(6):2718–2728. PMID: 7915741
Van Meir EG (1995) Cytokines and tumors of the central nervous system. Glia 15(3):264–288. https://doi.org/10.1002/glia.440150308
Walentynowicz KA, Ochocka N, Pasierbinska M, Wojnicki K, Stepniak K, Mieczkowski J, Ciechomska IA, Kaminska B (2018, Jun 15) In search for reliable markers of glioma-induced polarization of microglia. Front Immunol 9:1329. https://doi.org/10.3389/fimmu.2018.01329. eCollection 2018. PubMed PMID: 29963047; PubMed Central PMCID: PMC6013650
Wagner S, Czub S, Greif M, Vince GH, Süss N, Kerkau S, Rieckmann P, Roggendorf W, Roosen K, Tonn JC (1999 Jul 2) Microglial/macrophage expression of interleukin 10 in humanglioblastomas. Int J Cancer 82(1):12–16. https://doi.org/10.1002/(sici)1097-0215(19990702)82:1<12::aid-ijc3>3.0.co;2-o
Wang SC, Hong JH, Hsueh C, Chiang CS (2012) Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model. Lab Investig 92(1):151–162. https://doi.org/10.1038/labinvest.2011.128
Wang L, Zhang C, Zhang Z, Han B, Shen Z, Li L, Liu S, Zhao X, Ye F, Zhang Y (2018) Specific clinical and immune features of CD68 in glioma via 1,024 samples. Cancer Manag Res 10:6409–6419. https://doi.org/10.2147/CMAR.S183293
Watters JJ, Schartner JM, Badie B (2005) Microglia function in brain tumors. J Neurosci Res 81:447–455. https://doi.org/10.1002/jnr.20485
Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, Henriksson R, Le Rhun E, Balana C, Chinot O, Bendszus M, Reijneveld JC, Dhermain F, French P, Marosi C, Watts C, Oberg I, Pilkington G, Baumert BG, Taphoorn MJB, Hegi M, Westphal M, Reifenberger G, Soffietti R, Wick W, European Association for Neuro-Oncology (EANO) (2017) Task force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 18(6):e315–e329. https://doi.org/10.1016/S1470-2045(17)30194-8
Weller M, Le Rhun E, Preusser M, Tonn JC, Roth P (2019) How we treat glioblastoma. ESMO Open 4(Suppl 2):e000520
Wes PD, Holtman IR, Boddeke EW, Möller T, Eggen BJ (2016) Next generation transcriptomics and genomics elucidate biological complexity of microglia in health and disease. Glia 64(2):197–213. https://doi.org/10.1002/glia.22866
Westwood JA, Darcy PK, Kershaw MH (2013) Environmental enrichment does not impact on tumor growth in mice. F1000 Res 2:140. https://doi.org/10.12688/f1000research.2-140.v1
Wilmotte R, Burkhardt K, Kindler V, Belkouch MC, Dussex G, Nd T, Walker PR, Dietrich PY (2005) B7-homolog 1 expression by human glioma: a new mechanism of immune evasion. Neuroreport 16(10):1081–1085. https://doi.org/10.1097/00001756-200507130-00010
Wink MR, Lenz G, Braganhol E, Tamajusuku AS, Schwartsmann G, Sarkis JJ, Battastini AM (2003) Altered extracellular ATP, ADP and AMP catabolism in glioma cell lines. Cancer Lett 198(2):211–218. https://doi.org/10.1016/s0304-3835(03)00308-2
Wintterle S, Schreiner B, Mitsdoerffer M, Schneider D, Chen L, Meyermann R, Weller M, Wiendl H (2003) Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res 63(21):7462–7467
Wu A, Wei J, Kong LY, Wang Y, Priebe W, Qiao W, Sawaya R, Heimberger AB (2010) Glioma cancer stem cells induce immunosuppressive macrophages/microglia. Neuro-Oncology 12:1113–1125. https://doi.org/10.1093/neuonc/noq082
Xu R, Li C, Wu Y, Shen L, Ma J, Qian J, Ge J (2017) Role of KCa3.1 channels in macrophage polarization and its relevance in atherosclerotic plaque instability. ArteriosclerThrombVasc Biol 37(2):226–236. https://doi.org/10.1161/ATVBAHA.116.308461
Yan J, Kong LY, Hu J, Gabrusiewicz K, Dibra D, **a X, Heimberger AB, Li S (2015) FGL2 as a multimodality regulator of tumor-mediated immune suppression and therapeutic target in Gliomas. J Natl Cancer Inst 107(8):pii: djv137. https://doi.org/10.1093/jnci/djv137
Ye XZ, Xu SL, **n YH, Yu SC, ** YF, Chen L, **ao HL, Wang B, Yi L, Wang QL, Jiang XF, Yang L, Zhang P, Qian C, Cui YH, Zhang X, Bian XW (2012) Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-β1 signaling pathway. J Immunol 189(1):444–453. https://doi.org/10.4049/jimmunol.1103248
Yeh WL, Lu DY, Liou HC, Fu WM (2012) A forward loop between glioma and microglia: glioma-derived extracellular matrix-activated microglia secrete IL-18 to enhance the migration of glioma cells. J Cell Physiol 227(2):558–568. https://doi.org/10.1002/jcp.22746
Zhai H, Heppner FL, Tsirka SE (2011) Microglia/macrophages promote glioma progression. Glia 59(3):472–485. https://doi.org/10.1002/glia.21117
Zhang J, Sarkar S, Cua R, Zhou Y, Hader W, Yong VW (2012) A dialog between glioma and microglia that promotes tumor invasiveness through theCCL2/CCR2/interleukin-6 axis. Carcinogenesis 33(2):312–319. https://doi.org/10.1093/carcin/bgr289
Zhang I, Alizadeh D, Liang J, Zhang L, Gao H, Song Y, Ren H, Ouyang M, Wu X, D’Apuzzo M, Badie B (2016a) Characterization of Arginase expression in Glioma-associated microglia and macrophages. PLoS One 11(12):e0165118. https://doi.org/10.1371/journal.pone.0165118
Zhang M, Hutter G, Kahn SA, Azad TD, Gholamin S, Xu CY, Liu J, Achrol AS, Richard C, Sommerkamp P, Schoen MK, McCracken MN, Majeti R, Weissman I, Mitra SS, Cheshier SH (2016b) Anti-CD47 treatment stimulates phagocytosis of glioblastoma by M1 and M2 polarized macrophages and promotes M1 polarized macrophages in vivo. PLoS One 11(4):e0153550. https://doi.org/10.1371/journal.pone.0153550
Zhou X, Spittau B, Krieglstein K (2012) TGFβ signalling plays an important role in IL4-induced alternative activation of microglia. J Neuroinflammation 9:210. https://doi.org/10.1186/1742-2094-9-210
Zusso M, Methot L, Lo R, Greenhalgh AD, David S, Stifani S (2012) Regulation of postnatal forebrain amoeboid microglial cell proliferation and development by the transcription factor Runx1. J Neurosci 32:11285–11298. https://doi.org/10.1523/JNEUROSCI.6182-11.2012
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Catalano, M., D’Alessandro, G., Trettel, F., Limatola, C. (2020). Role of Infiltrating Microglia/Macrophages in Glioma. In: Barańska, J. (eds) Glioma Signaling. Advances in Experimental Medicine and Biology, vol 1202. Springer, Cham. https://doi.org/10.1007/978-3-030-30651-9_14
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