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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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Kind, L., & Kursula, P. (2018) · Amino Acids · doi:10.1007/s00726-018-2682-8 · Cited by 28
Microglia in Cancer: For Good or for Bad?
da Fonseca, A. C. C., do Amaral, R. F., Garcia, C., Geraldo, L. H., Matias, D., & Lima, F. R. S. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-40764-7_12 · Cited by 26
Immune surveillance of brain metastatic cancer cells is mediated by IFITM1
She, X., Shen, S., Chen, G., Gao, Y., Ma, J., Gao, Y., Liu, Y., Gao, G., Zhao, Y. F., Wang, C., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022111112 · Cited by 24
“…costimulatory molecules, which are involved in antigen presentation and the activation of the adaptive immune system, implying that the brain metastatic microenvironment is able to regulate the adaptive immune response (Yang et al, 2010; Schulz et al, 2020; Klemm et al, 2021; Niesel et al, 2021).”
BackgroundCAR T-cells to treat brain tumors
Guzman, G., Pellot, K., Reed, M. R., & Rodriguez, A. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.02.014 · Cited by 27
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“…injury (Eric Thomas 1992; Rock et al. 2004), and increase its proliferation (Eliason et al. 2002), motility (Carbonell et al. 2005), phagocytic activity (Schroeter et al. 1997; Zhang et al. 2001), and release of cytokines and reactive oxygen (Liu et al. 1998; Horvath et al. 2008; Yang et al. 2010).”
Therapeutic strategies of recurrent glioblastoma and its molecular pathways ‘Lock up the beast’
El-khayat, S. M., & Arafat, W. O. (2021) · ecancermedicalscience · doi:10.3332/ecancer.2021.1176 · Cited by 25
“The BBB breakdown allows CD8 + T cells to migrate to the CNS, and stimulation of the innate and adaptive immune responses which produce cytokines and chemokines to recruit lymphocytes and up-regulate immune-modularity markers on T-cell surfaces [77].”
BackgroundAhuja, S., & Lazar, I. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.646043 · Cited by 24
“Red-Cell cycle (74); Green-Chromosome organization (67); Turquoise-ECM organization (22); Dark yellow-PTMs (69); Brown-Signaling by RTK/cytoskeletal”
BackgroundMicroglia and microglial-based receptors in the pathogenesis and treatment of Alzheimer’s disease
Wang, Z., & Weaver, D. F. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109070 · Cited by 26
Chikungunya Immunopathology as It Presents in Different Organ Systems
Traverse, E. M., Millsapps, E. M., Underwood, E. C., Hopkins, H. K., Young, M., & Barr, K. L. (2022) · Viruses · doi:10.3390/v14081786 · Cited by 27
“Other important immune cells, in addition to astrocytes, are microglia, which are the macrophages of the brain [60].”
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Role of AHR in the control of GBM-associated myeloid cells
Gabriely, G., & Quintana, F. J. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.05.014 · Cited by 26
“Indeed, these cells comprise the predominant immune cell population in the GBM parenchyma [9, 10] and their abundance correlates with the GBM grade [11–13].”
BackgroundImmune Cell Infiltrates in Atypical Teratoid/Rhabdoid Tumors
Lu, J., Wilson, B. A., Yong, V. W., Pugh, J. A., & Mehta, V. (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s031716710001533x · Cited by 24
Natural killer cells in the brain tumor microenvironment: Defining a new era in neuro-oncology
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Metastatic Melanoma to the Brain: Surgery and Radiation Is Still the Standard of Care
Nicholas, S. E., Mathios, D., Jackson, C. M., & Lim, M. K. (2013) · Current Treatment Options in Oncology · doi:10.1007/s11864-013-0228-6 · Cited by 23
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Antibody, T-cell and Dendritic Cell Immunotherapy for Malignant Brain Tumors
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Immune check-point in glioblastoma multiforme
Felice, F. D., Pranno, N., Marampon, F., Musio, D., Salducci, M., Polimeni, A., & Tombolini, V. (2019) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.03.019 · Cited by 22
Intrinsic protective mechanisms of the neuron-glia network against glioma invasion
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“Microglia are resident macrophages that migrate into the brain early in development and differentiate into the ramified type [58].”
Neuroimmune interactions in painful TMD: Mechanisms and treatment implications
Yi, Y., Zhou, X., Xiong, X., & Wang, J. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0621-731rr · Cited by 21
Stonedahl, S., Leser, J. S., Clarke, P., & Tyler, K. L. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.00685-22 · Cited by 22
Anti-Inflammatory Action of Dexmedetomidine on Human Microglial Cells
Yamazaki, S., Yamaguchi, K., Someya, A., Nagaoka, I., & Hayashida, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710096 · Cited by 22
“Microglia are located in the central nervous system (CNS) and interact with neural synapses.”
BackgroundInfluentialChu, W., Phan, C., Lim, S. J., & Babji, A. S. (2022) · Food Science and Human Wellness · doi:10.1016/j.fshw.2022.10.021 · Cited by 24
Neuroinflammation in Glioblastoma: The Role of the Microenvironment in Tumour Progression
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“The intracranial immune responses modulated by microglia may be much more diverse and dynamic than previously thought and may result in containment and exacerbation during the malignant process [9, 13, 14].”
BackgroundCharacterization of Inflammatory Changes Associated with Canine Oligodendroglioma
Sloma, E. A., Creneti, C. T., Erb, H. N., & Miller, A. D. (2015) · Journal of Comparative Pathology · doi:10.1016/j.jcpa.2015.05.003 · Cited by 21
Exploitation of microRNAs by Japanese Encephalitis virus in human microglial cells
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“Microglia has been reported as a reservoir for JEV infection.(9) The activated microglial cells release cytokines and chemokines, which facilitate the inflammation.”
BackgroundBrain and Pituitary Response to Vaccination in Gilthead Seabream (Sparus aurata L.)
Liu, X., Khansari, A. R., Teles, M., Martı́nez-Rodrı́guez, G., Zhang, Y. G., Mancera, J. M., Reyes‐López, F. E., & Tort, L. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00717 · Cited by 20
Mechanisms of action of retinal microglia in diabetic retinopathy (Review)
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“In addition, excessive suppression of microglial activation and potential reduction of inflammation may compromise the normal immune surveillance capacity of microglia, increasing susceptibility to infections (171).”
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Alzheimer Disease and Cellular Mechanisms of Memory Storage
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“In the adult brain, activated microglia may mediate the immune cellYspecific functions, including the functions of antigen-presenting cells (168, 169).”
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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