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The role of microglia in central nervous system immunity and glioma immunology
Open accessAbstract
The central nervous system (CNS) historically has been considered an immune-privileged organ, lacking a lymphatic system and shielded from the circulatory system by the blood-brain barrier. Microglia are an abundant portion of the CNS cell population, comprising 5% to 20% of the total glial cell population, and are as numerous as neurons. A crucial function of microglia is the ability to generate significant innate and adaptive immune responses. Microglia are involved in first line innate immunity of the CNS. Proper antigen presentation is critical in the generation of specific, durable responses by the adaptive immune system, and requires interaction between the T cell receptor and processed antigen peptide presented on major histocompatibility complex (MHC) molecules by the antigen presenting cells (APC). Microglia also have a large regulatory role in CNS immunity. Histopathologic studies of glioma tissue have consistently shown high levels of infiltrating microglia. Microglia are also localized diffusely throughout the tumor, rather than to the areas of necrosis, and phagocytosis of glioma cells or debris by microglia is not observed. Recent evidence indicates that glioma-infiltrating microglia/macrophages might be promoting tumor growth by facilitating immunosuppression of the tumor microenvironment. When activated, microglia can be potent immune effector cells, able to perform a broad range of functions, and they mediate both innate and adaptive responses during CNS injury and disease while remaining quiescent in the steady state. Their versatility in bridging the gap between the immune-privileged CNS and the peripheral immune system, in addition to their significant numbers in gliomas, makes them an attractive candidate in immunotherapy for gliomas. An enhanced understanding of microglia-glioma interaction may provide better methods to manipulate the glioma microenvironment to allow the generation of a specific and durable anti-glioma immunity. The role of microglia in CNS immunity is reviewed, with a focus on key advances made in glioma immunology.
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“Microglia, the resident mononuclear phagocytes of the CNS, play key roles in immune surveillance and defense [39], synaptic remodeling [40], and homeostasis [41].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [39]
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Cites
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827 · cited 1×
“As routine surveillance of the CNS, microglia, even in their quiescent form, continually monitor their microenvironment through pinocytosis and interaction with neurons [29].”
BackgroundTumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396 · cited 1×
“Resting microglia serve as poor APC [59]; however, activating stimuli induce microglia to robustly increase their expression of MHC [60] and costimulatory molecules [61].”
BackgroundHeterogeneity in the distribution and morphology of microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., Dri, P., & Gordon, S. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90229-w · Cited by 2,045
van Kooten, C., & Banchereau, J. (2000) · Journal of Leukocyte Biology · doi:10.1002/jlb.67.1.2 · Cited by 1,413 · cited 3×
“The CD40–CD40L interaction also induces microglia to increase the release of nitric synthase [56].”
BackgroundLoss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma
Parsa, A. T., Waldron, J. S., Panner, A., Crane, C. A., Parney, I. F., Barry, J. J., Cachola, K. E., Murray, J. C., Tihan, T., Jensen, M. C., et al. (2006) · Nature Medicine · doi:10.1038/nm1517 · Cited by 1,341 · cited 1×
“In normal brain, microglia express B7-H1, a potent immunosuppressive molecule that induces T cell apoptosis [93, 94].”
BackgroundSelf-citationMicroglia initiate central nervous system innate and adaptive immune responses through multiple TLRs
Olson, J. K., & Miller, S. D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3916 · Cited by 1,215 · cited 4×
“Mature microglia express a variety of macrophage-specific markers including Toll-like receptors (TLR) [22, 23], the integrin CD11b [24], and the glycoprotein of unknown function, F4/80.”
BackgroundInfluentialMicroglia: Intrinsic immuneffector cell of the brain
Gehrmann, J., Matsumoto, Y., & Kreutzberg, G. W. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(94)00015-h · Cited by 1,111 · cited 1×
“MHC molecules are generally restricted to microglia in low levels [6, 57, 58].”
BackgroundCytology & cellular pathology of the nervous system
Penfield, W. G. (1965) · Medical Entomology and Zoology · Cited by 1,035
Banati, R. B., Gehrmann, J., Schubert, P., & Kreutzberg, G. W. (1993) · Glia · doi:10.1002/glia.440070117 · Cited by 1,032 · cited 1×
“For example, microglia express TLR [22] and initiate innate responses with the production of cytokines, chemokines and nitric oxide (NO) [37, 38].”
BackgroundDown-Regulation of the Macrophage Lineage Through Interaction with OX2 (CD200)
Hoek, R. M., Ruuls, S. R., Murphy, C. A., Wright, G. J., Goddard, R., Zurawski, S. M., Blom, B., Homola, M. E., Streit, W. J., Brown, M. H., et al. (2000) · Science · doi:10.1126/science.290.5497.1768 · Cited by 1,022 · cited 3×
“Upon activation, microglia upregulate opsonic receptors including complement receptors (CR1, CR3, CR4) and Fc gamma receptors (I, II, III), which enhance phagocytic activity by binding to complement components and immunoglobulin fragments respectively [50, 51].”
BackgroundBroad Expression of Toll-Like Receptors in the Human Central Nervous System
Bsibsi, M., Ravid, R., Gveric, D. O., & van Noort, J. M. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.11.1013 · Cited by 1,000 · cited 4×
“Mature microglia express a variety of macrophage-specific markers including Toll-like receptors (TLR) [22, 23], the integrin CD11b [24], and the glycoprotein of unknown function, F4/80.”
BackgroundInfluentialMicroglial Activation and its Implications in the Brain Diseases
Dheen, S. T., Kaur, C., & Ling, E. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707780597961 · Cited by 968 · cited 1×
“The resting ramified microglia cells are activated by a variety of CNS pathologies, such as infection, injury, and neurodegenerative disease, by detecting lipopolysaccharide (LPS), beta-amyloid (Aβ), thrombin, IFN-γ, and other proinflammatory cytokines [36].”
BackgroundMolecular mechanisms of glioma invasiveness: the role of proteases
Rao, J. S. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1121 · Cited by 847 · cited 1×
“Their release into the tumor environment can help increase the spread of tumors by paving the road for proliferation of tumor cells [81].”
BackgroundTurnover of resident microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., & Gordon, S. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90500-2 · Cited by 709
Sedgwick, J. D., Schwender, S., Imrich, H., Dörries, R., Butcher, G. W., & ter Meulen, V. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7438 · Cited by 691
The origin and nature of ramified and amoeboid microglia: A historical review and current concepts
Ling, E., & Wong, W.-C. (1993) · Glia · doi:10.1002/glia.440070105 · Cited by 690 · cited 2×
“Microglia are classified according their morphology into three types: resting ramified, activated, and amoeboid phagocytic [21].”
BackgroundErratum: Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomão, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm0902-1039c · Cited by 545
Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis
Benveniste, E. N. (1997) · Journal of Molecular Medicine · doi:10.1007/s001090050101 · Cited by 532
Chemokine Expression by Glial Cells Directs Leukocytes to Sites of Axonal Injury in the CNS
Babcock, A. A., Kuziel, W. A., Rivest, S., & Owens, T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07922.2003 · Cited by 472 · cited 2×
“MCP-1 is produced by glioma cells, and microglia express a specific MCP-1 receptor, CCR2 [75, 76].”
BackgroundBrain microglia constitutively express β-2 integrins
Akiyama, H., & McGeer, P. L. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90055-r · Cited by 430 · cited 2×
“Dick AD, Ford AL, Forrester JV, et al. Flow cytometric identification of a minority population of MHC class II positive cells in the normal rat retina distinct from CD45lowCD11b/c+CD4low parenchymal microglia.”
Brain Dendritic Cells and Macrophages/Microglia in Central Nervous System Inflammation
Fischer, H., & Reichmann, G. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.4.2717 · Cited by 408 · cited 1×
“Fischer and Reichmann have demonstrated that in vitro incubation of purified microglia with GM-CSF increases microglia cell size and induces a heterogeneous population that contains cells resembling other tissue macrophages [35].”
BackgroundWright, G. J., Puklavec, M. J., Willis, A. C., Hoek, R. M., Sedgwick, J. D., Brown, M. H., & Barclay, A. N. (2000) · Immunity · doi:10.1016/s1074-7613(00)00023-6 · Cited by 388 · cited 1×
“In addition, Hoek and colleagues have implicated a membrane-bound glycoprotein, OX2 or CD200, expressed on neurons as a key regulator of microglia [32, 33].”
BackgroundSchilling, M., Besselmann, M., Leonhard, C., Mueller, M., Ringelstein, E. B., & Kiefer, R. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00082-7 · Cited by 375 · cited 1×
“The specific sequence of events demonstrating that microglia activation precedes peripheral cell infiltration has been demonstrated in bone marrow chimeric mice in an elegant study by Schilling and colleagues [49].”
BackgroundKennedy, D. W., & Abkowitz, J. L. (1997) · Blood · doi:10.1182/blood.v90.3.986 · Cited by 342
Distribution and characterization of microglia/macrophages in human brain tumors
Roggendorf, W., Strupp, S., & Paulus, W. (1996) · Acta Neuropathologica · doi:10.1007/s004010050520 · Cited by 319
Ferrer, I., Bernet, E., Soriano, E., del Rı́o, J. A., & Fonseca, M. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90281-8 · Cited by 317 · cited 1×
“Microglia also show transitory phagocytosis during CNS ontogeny to clear apoptotic neuronal cell bodies [52].”
BackgroundTransforming growth factor-beta suppresses activation and proliferation of microglia in vitro.
Suzumura, A., Sawada, M., Yamamoto, H., & Marunouchi, T. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.4.2150 · Cited by 305 · cited 1×
“In particular, TGF-β2 inhibits proliferation and secretion of proinflammatory cytokines by microglia and lymphocytes [92].”
BackgroundTsai, J., Goldman, C. K., & Gillespie, G. Y. (1995) · Journal of neurosurgery · doi:10.3171/jns.1995.82.5.0864 · Cited by 281 · cited 3×
“Lafuente JV, Adan B, Alkiza K, et al. Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor-beta (PDGFR-beta) in human gliomas.”
BackgroundHematopoietic origin of microglial and perivascular cells in brain
Hess, D. C., Abe, T., Hill, W., Martin-Studdard, A., Carothers, J., Masuya, M., Fleming, P. A., Drake, C. J., & Ogawa, M. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2003.11.005 · Cited by 281 · cited 2×
“In the perinatal brain, the amoeboid phagocytic microglia are the predominant form [27].”
BackgroundAloisi, F., Ria, F., Penna, G., & Adorini, L. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.10.4671 · Cited by 276
Microglia induce CD4 T lymphocyte final effector function and death.
Ford, A. L., Foulcher, E., Lemckert, F. A., & Sedgwick, J. D. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.5.1737 · Cited by 260 · cited 8×
“Proper antigen presentation is critical in the generation-specific durable responses by the adaptive immune system, and requires interaction between the T cell receptor and processed antigen peptide presented on MHC molecules by the APCs.”
BackgroundInfluentialFloden, A. M., Li, S., & Combs, C. K. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4998-04.2005 · Cited by 254
Macrophages in experimental and human brain tumors
Morantz, R. A., Wood, G. W., Foster, M., Clark, M., & Gollahon, K. A. (1979) · Journal of neurosurgery · doi:10.3171/jns.1979.50.3.0305 · Cited by 239 · cited 1×
“Historically, the recruitment of microglia in gliomas was postulated as evidence of the attempt by CNS to fend off dividing neoplastic cells [80].”
BackgroundHöftberger, R., Aboul‐Enein, F., Brück, W., Lucchinetti, C. F., Rodriguez, M., Schmidbauer, M., Jellinger, K. A., & Lassmann, H. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00496.x · Cited by 229 · cited 1×
“MHC molecules are generally restricted to microglia in low levels [6, 57, 58].”
BackgroundThe central nervous system as an immunocompetent organ: role of glial cells in antigen presentation
Shrikant, P., & Benveniste, E. N. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.5.1819 · Cited by 229 · cited 1×
“Additionally, in vivo and in vitro studies have demonstrated that IFN-γ induces and maintains expression of MHC class II and adhesion/ costimulatory molecules on microglia to maintain T cell stimulation [62].”
BackgroundSimone, R. D., Giampaolo, A., Giometto, B., Gallo, P., Levi, G., Peschle, C., & Aloisi, F. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199503000-00004 · Cited by 201 · cited 1×
“Resting microglia serve as poor APC [59]; however, activating stimuli induce microglia to robustly increase their expression of MHC [60] and costimulatory molecules [61].”
BackgroundCD28/CTLA-4 and CD80/CD86 families
Slavik, J. M., Hutchcroft, J. E., & Bierer, B. E. (1999) · Immunologic Research · doi:10.1007/bf02786473 · Cited by 200 · cited 2×
“1, CD40, CD80, and CD86 expressed on the surface of APC and specific counter-receptors on T cells [55, 56].”
BackgroundRole of microglia in glioma biology
Badie, B., & Schartner, J. M. (2001) · Microscopy Research and Technique · doi:10.1002/jemt.1125 · Cited by 184 · cited 3×
“Recent evidence indicates that glioma-infiltrating microglia/macrophages might be promoting tumor growth by facilitating immunosuppression of the tumor microenvironment [16].”
BackgroundInfluentialSiegrist, C., Barrios, C. S., Martínez, X., Brandt, C., Berney, M., Córdova, M., Kovařík, J., & Lambert, P. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199812)28:12 · Cited by 184
Parney, I. F., Petruk, K. C., Hao, C., Roa, W., Turner, J., & Ramsay, D. A. (2002) · Acta Neuropathologica · doi:10.1007/s004010100448 · Cited by 181 · cited 3×
“Microglia are also localized diffusely throughout the tumor, and not to the areas of necrosis, and phagocytosis of glioma cells or debris by microglia is not observed [1].”
BackgroundFlow cytometry and in vitro analysis of human glioma–associated macrophages
Parney, I. F., Waldron, J. S., & Parsa, A. T. (2009) · Journal of neurosurgery · doi:10.3171/2008.7.jns08475 · Cited by 179 · cited 2×
“Co-culture of human peripheral blood mononuclear cells with human glioma lines caused glioma-conditioned monocytes to reduce phagocytic activity [84].”
BackgroundSelf-citationProjections of auditory cortex to the medial geniculate body of the cat
Winer, J. A., Diehl, J. J., & Larue, D. T. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20010129)430:1 · Cited by 174
Phagocytic Response in Photochemically Induced Infarction of Rat Cerebral Cortex
Schroeter, M., Jander, S., Huitinga, I., Witte, O. W., & Stoll, G. (1997) · Stroke · doi:10.1161/01.str.28.2.382 · Cited by 169
Human Glioma-derived Interleukin-10 Inhibits Antitumor Immune Responses In Vitro
Hishii, M., Nitta, T., Ishida, H., Ebato, M., Kurosu, A., Yagita∥, H., Sato, K., & Okumura, K. (1995) · Neurosurgery · doi:10.1227/00006123-199512000-00016 · Cited by 168 · cited 1×
“IL-10 in turn inhibits cytotoxic T cell function, further contributing to the immunoresistant phenotype of glioma cells [89].”
BackgroundMicroglia promote glioma migration
Bettinger, I., Thanos, S., & Paulus, W. (2002) · Acta Neuropathologica · doi:10.1007/s00401-001-0472-x · Cited by 165
Magnus, T., Schreiner, B., Korn, T., Jack, C. S., Guo, H., Antel, J. P., Ifergan, I., Chen, L., Bischof, F., Bar‐Or, A., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4794-04.2005 · Cited by 164 · cited 1×
“In normal brain, microglia express B7-H1, a potent immunosuppressive molecule that induces T cell apoptosis [93, 94].”
BackgroundAloisi, F., Simone, R. D., Cabezas, S. C., Penna, G., & Adorini, L. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.4.1705 · Cited by 153
Glioma Immunology and Immunotherapy
Parney, I. F., Hao, C., & Petruk, K. C. (2000) · Neurosurgery · doi:10.1097/00006123-200004000-00002 · Cited by 145 · cited 1×
“Glioma cells produce anti-inflammatory cytokines such as IL-6 and TGF-β2 and PGE2 along with producing tumor growth promoting cytokines such as IL-1 and bFGF [1, 91].”
BackgroundNeuronal Control of MHC Class II Inducibility in Rat Astrocytes and Microglia
Neumann, H., Boucraut, J., Hahnel, C., Misgeld, T., & Wekerle, H. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01552.x · Cited by 142 · cited 6×
“Additionally, in vivo and in vitro studies have demonstrated that IFN-γ induces and maintains expression of MHC class II and adhesion/ costimulatory molecules on microglia to maintain T cell stimulation [62].”
BackgroundInfluentialAstrocytic Regulation of Human Monocytic/Microglial Activation
Kostianovsky, A. M., Maier, L. M., Anderson, R. C. E., Bruce, J. N., & Anderson, D. E. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.8.5425 · Cited by 142 · cited 2×
“Kostianovsky and colleagues demonstrated in vitro that glioblastoma cells down regulated the production of the proinflammatory cytokine TNF-α by microglia when stimulated with LPS or β-amyloid [70].”
BackgroundSuccessful treatment of intracranial gliomas in rat by oligodeoxynucleotides containing CpG motifs.
Carpentier, A. F., Xie, J., Mokhtari, K., & Delattre, J. (2000) · PubMed · Cited by 138
Impaired capacity for upregulation of MHC class II in tumor‐associated microglia
Schartner, J. M., Hagar, A. R., Handel, M. M. V., Zhang, L., Nadkarni, N. V., & Badie, B. (2005) · Glia · doi:10.1002/glia.20201 · Cited by 134
Modulation of human microglial cell superoxide production by cytokines
Chao, C. C., Hu, S., & Peterson, P. K. (1995) · Journal of Leukocyte Biology · doi:10.1002/jlb.58.1.65 · Cited by 131 · cited 1×
“In addition, the cytotoxic functions of microglia are carried out by release of superoxide radicals and NO into the microenvironment in response to pathogens and cytokine stimulation [54].”
BackgroundMacrophages in experimental and human brain tumors
Morantz, R. A., Wood, G. W., Foster, M., Clark, M., & Gollahon, K. A. (1979) · Journal of neurosurgery · doi:10.3171/jns.1979.50.3.0298 · Cited by 131
Apoptosis of inflammatory cells in immune control of the nervous system: Role of glia
Pender, M. P., & Rist, M. (2001) · Glia · doi:10.1002/glia.1103 · Cited by 131
Upregulation of RANTES Gene Expression in Neuroglia by Japanese Encephalitis Virus Infection
Chen, C., Chen, J., Chen, S., Liao, S., & Raung, S. (2004) · Journal of Virology · doi:10.1128/jvi.78.22.12107-12119.2004 · Cited by 131 · cited 2×
“Specifically, cytokines released by activated microglia include interleukin (IL)-1 [39], IL-6 [40] and tumor necrosis factor-alpha (TNF-α) [41], as well as monocyte chemoattractant protein-1 (MCP-1) [42], macrophage inflammatory protein-1 [43, 44] and RANTES [45], and chemokines for lymphocyte recruitment.”
BackgroundDick, A. D., Ford, A. L., Forrester, J. V., & Sedgwick, J. D. (1995) · British Journal of Ophthalmology · doi:10.1136/bjo.79.9.834 · Cited by 129 · cited 2×
“These populations of microglial cells take on APC activity by expression of MHC class II molecules [25].”
BackgroundIncreased Morphological Diversity of Microglia in the Activated Hypothalamic Supraoptic Nucleus
Ayoub, A. E., & Salm, A. K. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07759.2003 · Cited by 122
Expression of Fas ligand by microglia: possible role in glioma immune evasion
Badie, B., Schartner, J. M., Prabakaran, S., Paul, J. S., & Vorpahl, J. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00361-7 · Cited by 119 · cited 1×
“Microglia in intracranial tumors express FASL and inhibition of FASL leads to a dramatic increase in the number of peripheral immune effector cells seen within tumors [69, 96].”
BackgroundKamei, Y., Inagaki, N., Nishizawa, M., Tsutsumi, O., Taketani, Y., & Inagaki, M. (1998) · Glia · doi:10.1002/(sici)1098-1136(199807)23:3 · Cited by 114
Peress, N. S., Fleit, H. B., Perillo, E., Kuljiš, R. O., & Pezzullo, C. (1993) · Journal of Neuroimmunology · doi:10.1016/0165-5728(93)90060-c · Cited by 111
Microglia-derived macrophages in early multiple sclerosis plaques
Li, H., Cuzner, M. L., & Newcombe, J. (1996) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1996.tb00896.x · Cited by 111 · cited 2×
“This cooperative enhancement of costimulation between microglia and T cells has been demonstrated in animal models of multiple sclerosis [34].”
BackgroundBadie, B., Schartner, J. M., Klaver, J., & Vorpahl, J. (1999) · Neurosurgery · doi:10.1097/00006123-199905000-00075 · Cited by 109
Trần, Wolz, Egensperger, Kösel, Imai, Bise, Kohsaka, Mehraein, & Graeber (1998) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.1998.00120.x · Cited by 94 · cited 1×
“Although MHC molecule expression is seen on microglia within glioma tissues [85, 86], they appear deficient in proper antigen presentation [87] for cytotoxic and helper T cell activation.”
BackgroundYang, I., Kremen, T. J., Giovannone, A. J., Paik, E., Odesa, S. K., Prins, R. M., & Liau, L. M. (2004) · Journal of neurosurgery · doi:10.3171/jns.2004.100.2.0310 · Cited by 84 · cited 1×
“Within the CNS under resting states, MHC class I and II expression is generally absent or minimally present [3, 57].”
BackgroundSelf-citationRoth, A. B., Schaffner, W., & Hertel, C. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990801)57:3 · Cited by 81
The mononuclear cell infiltrate compared with survival in high-grade astrocytomas
Rossi, M. I., Jones, N., Candy, E., Nicoll, J. A. R., Compton, J. S., Hughes, J. T., Esiri, M. M., Moss, T., Cruz-Sánchez, F. F., & Coakham, H. B. (1989) · Acta Neuropathologica · doi:10.1007/bf00688208 · Cited by 78
Microglia only weakly present glioma antigen to cytotoxic T cells
Flügel, A., Labeur, M. S., Grasbon‐Frodl, E., Kreutzberg, G. W., & Graeber, M. B. (1999) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(99)00020-9 · Cited by 73 · cited 1×
“Although MHC molecule expression is seen on microglia within glioma tissues [85, 86], they appear deficient in proper antigen presentation [87] for cytotoxic and helper T cell activation.”
BackgroundCarpentier, A. F. (2003) · Frontiers in bioscience · doi:10.2741/934 · Cited by 72 · cited 4×
“For example, Carpentier and colleagues demonstrated long-term survival in animals with glioma using single intratumoral injection of CpG oligodeoxynucleotide, an immuno-stimulatory sequence that signals through TLR9 to induce the production of IFN-α, IFN-β, IL-12, and TNF-α [97, 98].”
BackgroundInfluentialLafuente, J. V., Adan, B., Alkiza, K., Garibi, J., Rossi, M., & Ff, C.-S. (1999) · Journal of Molecular Neuroscience · doi:10.1385/jmn:13:1-2:177 · Cited by 71
Colony stimulating factor-1 expression in human glioma
Alterman, R. L., & Stanley, E. R. (1994) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815350 · Cited by 70
Badie, B., Schartner, J. M., Paul, J. S., Bartley, B., Vorpahl, J., & Preston, J. K. (2000) · Journal of neurosurgery · doi:10.3171/jns.2000.93.4.0634 · Cited by 69 · cited 2×
“Flow cytometry studies by Badie and colleagues demonstrated that as many as one-third of cells of glioma tissues express resident microglia markers, consisting of the largest population of immune cells [2].”
BackgroundBaldwin, A. C., & Kielian, T. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.02.002 · Cited by 69 · cited 1×
“These changes in turn decrease the stringency of the blood-brain barrier, allowing entry of soluble factors and peripheral immune cells [46], including macrophages, natural killer cells and lymphocytes [47, 48].”
BackgroundBadie, B., Bartley, B., & Schartner, J. M. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00350-8 · Cited by 68 · cited 1×
“In contrast, the expressions of MHC class II and costimulatory B7 molecules were significantly increased when freshly isolated microglia were cultured in the absence of glioma cells [88].”
BackgroundTakami, S., Nishikawa, H., Minami, M., Nishiyori, A., Sato, M., Akaike, A., & Satoh, M. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00338-8 · Cited by 67 · cited 1×
“Specifically, cytokines released by activated microglia include interleukin (IL)-1 [39], IL-6 [40] and tumor necrosis factor-alpha (TNF-α) [41], as well as monocyte chemoattractant protein-1 (MCP-1) [42], macrophage inflammatory protein-1 [43, 44] and RANTES [45], and chemokines for lymphocyte recruitment.”
BackgroundSuzumura, A., Sawada, M., & Marunouchi, T. (1996) · Brain Research · doi:10.1016/0006-8993(95)01535-3 · Cited by 56 · cited 2×
“Microglia and local immune suppression by glioma Glioma cells produce anti-inflammatory cytokines such as IL-6 and TGF-β2 and PGE2 along with producing tumor growth promoting cytokines such as IL-1 and bFGF [1, 91].”
BackgroundReactive microglia in dysmyelination and demyelination
Zhang, S., Goetz, B. D., Carré, J., & Duncan, I. D. (2001) · Glia · doi:10.1002/glia.1045 · Cited by 51 · cited 2×
“until stimuli from injury, infection or neurodegenerative process activate their transformation into amoeboid phagocytic cells [10, 11].”
BackgroundImplication of macrophages in tumor rejection induced by CpG-oligodeoxynucleotides without antigen.
Auf, G., Carpentier, A. F., Chen, L., Clanche, C. L., & Delattre, J. (2001) · PubMed · Cited by 50
Kohji, T., & Matsumoto, Y. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00238-1 · Cited by 48 · cited 2×
“Microglia in turn also express FAS molecules which, upon binding FASL, leads to their own apoptosis [66].”
BackgroundT-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy
Walker, D., Chuah, T., Rist, M., & Pender, M. P. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.03.006 · Cited by 48 · cited 1×
“Microglia in intracranial tumors express FASL and inhibition of FASL leads to a dramatic increase in the number of peripheral immune effector cells seen within tumors [69, 96].”
BackgroundCarbonell, W. S., Murase, S., Horwitz, A. F., & Mandell, J. W. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-5 · Cited by 47
Lu, J., Moochhala, S., Kaur, C., & Ling, E. (2001) · Journal of Neurotrauma · doi:10.1089/089771501750170976 · Cited by 45 · cited 1×
“These changes in turn decrease the stringency of the blood-brain barrier, allowing entry of soluble factors and peripheral immune cells [46], including macrophages, natural killer cells and lymphocytes [47, 48].”
BackgroundBarnum, S. R. (1999) · Molecular Medicine · doi:10.1007/bf03402070 · Cited by 45 · cited 1×
“Upon activation, microglia upregulate opsonic receptors including complement receptors (CR1, CR3, CR4) and Fc gamma receptors (I, II, III), which enhance phagocytic activity by binding to complement components and immunoglobulin fragments respectively [50, 51].”
BackgroundSTAT6-independent production of IL-4 by mast cells
Sherman, M. A., Secor, V. H., Lee, S. K., Lopez, R. D., & Brown, M. A. (1999) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199904)29:04 · Cited by 45
Prat, E., Baron, P., Meda, L., Scarpini, E. A., Galimberti, D., Ardolino, G., Catania, A., & Scarlato, G. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)00966-6 · Cited by 44 · cited 1×
“MCP-1 is produced by glioma cells, and microglia express a specific MCP-1 receptor, CCR2 [75, 76].”
BackgroundNguyen, K. B., & Pender, M. P. (1998) · Acta Neuropathologica · doi:10.1007/s004010050763 · Cited by 40 · cited 1×
“A similar phenomenon is seen in animal models of multiple sclerosis – T cell debris undergoes phagocytosis by microglia [53].”
BackgroundExperimental Gliosarcoma Induces Chemokine Receptor Expression in Rat Brain
Galasso, J. M., Stegman, L. D., Blaivas, M., Harrison, J. K., Ross, B. D., & Silverstein, F. S. (2000) · Experimental Neurology · doi:10.1006/exnr.1999.7249 · Cited by 37 · cited 1×
“MCP-1 is produced by glioma cells, and microglia express a specific MCP-1 receptor, CCR2 [75, 76].”
BackgroundReaction of microglial cells in human astrocytomas (preliminary report).
Wierzba‐Bobrowicz, T., Kuchna, I., & Matyja, E. (1994) · PubMed · Cited by 37
GM‐CSF and M‐CSF modulate β‐chemokine and HIV‐1 expression in microglia
Si, Q., Cosenza, M., Zhao, M., Goldstein, H., & Lee, S. C. (2002) · Glia · doi:10.1002/glia.10095 · Cited by 35
Local Neurochemicals and Site-Specific Immune Regulation in the CNS
McCluskey, L. P., & Lampson, L. A. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.3.177 · Cited by 34 · cited 1×
“A complex set of interactions exist between local stimulatory and inhibitory signals in shaping microglial responses: while some neurotransmitters like substance P enhance the active phenotype of microglia [30], electrically active neurons inhibit the increase in expression of MHC class II molecules on microglia in re…”
BackgroundSite-specific immune response to implanted gliomas
Proescholdt, M. A., Merrill, M. J., Ikejiri, B. L., Walbridge, S., Akbaşak, A., Jacobson, S., & Oldfield, E. H. (2001) · Journal of neurosurgery · doi:10.3171/jns.2001.95.6.1012 · Cited by 31 · cited 1×
“Although MHC molecule expression is seen on microglia within glioma tissues [85, 86], they appear deficient in proper antigen presentation [87] for cytotoxic and helper T cell activation.”
BackgroundCellular immune response in brain tumors.
Streit, W. J. (1994) · PubMed · Cited by 30
Modulation of Fas-Ligand (Fas-L) on human microglial cells: an in vitro study
Frigerio, S., Silei, V., Ciusani, E., Massa, G. A., Lauro, G. M., & Salmaggi, A. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00227-1 · Cited by 29 · cited 1×
“The FASL expression on microglia has been described in vitro [64, 65] and in mouse models of multiple sclerosis [66].”
BackgroundBrannan, C. A., & Roberts, M. R. (2004) · Glia · doi:10.1002/glia.20066 · Cited by 25
Suzuki, Y., Funakoshi, H., Machide, M., Matsumoto, K., & Nakamura, T. (2008) · Biomedical Research · doi:10.2220/biomedres.29.77 · Cited by 25
Glioma Immunology and Immunotherapy
Parney, I. F., Hao, C., & Petruk, K. C. (2000) · Neurosurgery · doi:10.1227/00006123-200004000-00002 · Cited by 22
Local proliferation of microglia cells in response to neocortical injury in vitro
Eliason, D. A., Cohen, S. A., Baratta, J. L., Yu, J. Z., & Robertson, R. T. (2002) · Developmental Brain Research · doi:10.1016/s0165-3806(02)00413-3 · Cited by 20 · cited 1×
“In the context of CNS insult or injury, microglia convert to an active phenotype, with increased proliferation [8], motility [9], and phagocytic activity [10, 11], and release cytokines and reactive oxygen species [12].”
BackgroundNakamichi, K., Saiki, M., Sawada, M., Yamamuro, Y., Morimoto, K., & Kurane, I. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03354.x · Cited by 17 · cited 1×
“For example, microglia express TLR [22] and initiate innate responses with the production of cytokines, chemokines and nitric oxide (NO) [37, 38].”
BackgroundDifferential microglial regulation in the human spinal cord under normal and pathological conditions
Stoll, M., Capper, D., Dietz, K., Warth, A., Schleich, A., Schlaszus, H., Meyermann, R., & Mittelbronn, M. G. A. (2006) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2006.00774.x · Cited by 15 · cited 2×
“MHC molecules are generally restricted to microglia in low levels [6, 57, 58].”
Background
Cited by
Sorted by citations
Zhuang, X., Xiang, X., Grizzle, W., Sun, D., Zhang, S., Axtell, R. C., Ju, S., Mu, J., Zhang, L., Steinman, L., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2011.164 · Cited by 1,356
Microglial cell origin and phenotypes in health and disease
Saijo, K., & Glass, C. K. (2011) · Nature Reviews Immunology · doi:10.1038/nri3086 · Cited by 1,100
“Regardless of their classification as M2-like or MDSC-like, glioma-associated microglia express low levels of MHC class II molecules, which are required to present tumour-specific antigens to T cell”
BackgroundEmerging therapies for glioblastoma: current state and future directions
Rong, L., Li, N., & Zhang, Z. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02349-7 · Cited by 546
“In adults, microglia account for approximately 10% of CNS cells and maintain a quiescent phenotype in the normal CNS, expressing low levels of MHC molecules and costimulatory molecules [43].”
BackgroundBidirectional Microglia–Neuron Communication in Health and Disease
Szepesi, Z., Manouchehrian, O., Bachiller, S., & Deierborg, T. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00323 · Cited by 459
Veerhuis, R., Nielsen, H. M., & Tenner, A. J. (2011) · Molecular Immunology · doi:10.1016/j.molimm.2011.04.003 · Cited by 436
“…immune effector cells and are able to produce cytokines and chemokines as well as to phagocytose up targets upon stimulation (Dong and Benveniste, 2001;Nielsen et al., 2010;Familian et al., 2007;Nielsen et al., 2009;Fraser et al., 2010;Bohlson et al., 2007;Yang et al., 2010;Watabe et al., 1989).”
Background
Metadata
- Authors
- Yang, I., Han, S. J., Kaur, G., Crane, C., & Parsa, A. T.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Journal of Clinical Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 17
- Issue
- 1
- Pages
- 6-10
- ISSN
- 0967-5868 (ISSN-L)
- PMC
- PMC3786731
- OpenAlex
- W2161737261
- Cited by
- 410
- References
- 101
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 26 · 2023: 33 · 2022: 41 · 2021: 26 · 2020: 23 · 2019: 24 · 2018: 15 · 2017: 19 · 2016: 22 · 2015: 23 · 2014: 23 · 2013: 27 · 2012: 27
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P50CA097257)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- microglia, central nervous system immunity, tumor microenvironment, immunosuppression, antigen presentation, T cell receptor, major histocompatibility complex, antigen-presenting cells, microglial activation, glioma immunotherapy, blood-brain barrier, immune privilege
- MeSH terms
- Animals, Brain Neoplasms, Cell Communication, Central Nervous System, Glioma, Humans, Immune Tolerance, Immunity, Innate, Immunologic Surveillance, Neuroimmunomodulation, Microglia, Adaptive Immunity
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