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Review
. 2021 Apr 7;11(4):466.
doi: 10.3390/brainsci11040466.

Immunomodulatory Effect of Microglia-Released Cytokines in Gliomas

Marika Lanza  1 , Giovanna Casili  1 , Michela Campolo  1 , Irene Paterniti  1 , Cristina Colarossi  2 , Marzia Mare  2 , Raffella Giuffrida  3 , Maria Caffo  4 , Emanuela Esposito  1 , Salvatore Cuzzocrea  1
Affiliations
Review

Immunomodulatory Effect of Microglia-Released Cytokines in Gliomas

Marika Lanza et al. Brain Sci. .

Abstract

Microglia, a type of differentiated tissue macrophage, are considered to be the most plastic cell population of the central nervous system (CNS). Microglia substantially contribute to the growth and invasion of tumor mass in brain tumors including glioblastoma (GB). In response to pathological conditions, resting microglia undergo a stereotypic activation process and become capable of phagocytosis, antigen presentation, and lymphocyte activation. Considering their immune effector function, it is not surprising to see microglia accumulation in almost every CNS disease process, including malignant brain tumors. Large numbers of glioma associated microglia and macrophages (GAMs) can accumulate within the tumor where they appear to have an important role in prognosis. GAMs constitute the largest portion of tumor infiltrating cells, contributing up to 30% of the entire glioma mass and upon interaction with neoplastic cells. GAMs acquire a unique phenotype of activation, including both M1 and M2 specific markers. It has been demonstrated that microglia possess a dual role: on one hand, microglia may represent a CNS anti-tumor response, which is inactivated by local secretion of immunosuppressive factors by glioma cells. On the other hand, taking into account that microglia are capable of secreting a variety of immunomodulatory cytokines, it is possible that they are attracted by gliomas to promote tumor growth. A better understanding of microglia-glioma interaction will be helpful in designing novel immune-based therapies against these fatal tumors. Concluding, as microglia significantly may contribute to glioma biology, favoring tumor growth and invasiveness, these cells represent a valuable alternative/additional target for the development of more effective treatments for gliomas.

Keywords: brain tumors; immunotherapy; microglia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Differentiation of microglia. The figure illustrates the differentiation of microglia into M1 and M2 subtypes, with the related functions for each.
Figure 2
Figure 2
Cross-talk between glioma cells and microglia.
See this image and copyright information in PMC

References

    1. Louis D.N., Ohgaki H., Wiestler O.D., Cavenee W.K., Burger P.C., Jouvet A., Scheithauer B.W., Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109. doi: 10.1007/s00401-007-0243-4. - DOI - PMC - PubMed
    1. Sasmita A.O., Wong Y.P., Ling A.P.K. Biomarkers and therapeutic advances in glioblastoma multiforme. Asia Pac. J. Clin. Oncol. 2018;14:40–51. doi: 10.1111/ajco.12756. - DOI - PubMed
    1. Razavi S.M., Lee K.E., Jin B.E., Aujla P.S., Gholamin S., Li G. Immune Evasion Strategies of Glioblastoma. Front. Surg. 2016;3:11. doi: 10.3389/fsurg.2016.00011. - DOI - PMC - PubMed
    1. Weathers S.P., Gilbert M.R. Current challenges in designing GBM trials for immunotherapy. J. Neurooncol. 2015;123:331–337. doi: 10.1007/s11060-015-1716-2. - DOI - PubMed
    1. Wrensch M., Minn Y., Chew T., Bondy M., Berger M.S. Epidemiology of primary brain tumors: Current concepts and review of the literature. Neuro Oncol. 2002;4:278–299. doi: 10.1093/neuonc/4.4.278. - DOI - PMC - PubMed

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