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  • Review Article
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Multifaceted microglia — key players in primary brain tumour heterogeneity

Nature Reviews Neurology volume 17, pages 243–259 (2021)Cite this article

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Abstract

Microglia are the resident innate immune cells of the immune-privileged CNS and, as such, represent the first line of defence against tissue injury and infection. Given their location, microglia are undoubtedly the first immune cells to encounter a developing primary brain tumour. Our knowledge of these cells is therefore important to consider in the context of such neoplasms. As the heterogeneous nature of the most aggressive primary brain tumours is thought to underlie their poor prognosis, this Review places a special emphasis on the heterogeneity of the tumour-associated microglia and macrophage populations present in primary brain tumours. Where available, specific information on microglial heterogeneity in various types and subtypes of brain tumour is included. Emerging evidence that highlights the importance of considering the heterogeneity of both the tumour and of microglial populations in providing improved treatment outcomes for patients is also discussed.

Key points

  • Brain tumours are heterogeneous and can now be subdivided into molecular subtypes based on genetic alterations.

  • These tumour subtypes contain tumour-associated microglia and/or macrophages that can vary in number and phenotype.

  • Microglia display acquired as well as intrinsic spatiotemporal heterogeneity (that is, reaction states and subtypes) that should be considered in the context of the tumour microenvironment.

  • Understanding the complexity of tumour-associated microglia and macrophage populations could have diagnostic value and generate novel avenues for therapeutic intervention.

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Fig. 1: Microglial subtypes have unique spatiotemporal distributions.
Fig. 2: TAM content in paediatric and adult brain tumours.
Fig. 3: Cell markers can discriminate resident microglia from infiltrating macrophages in the tumour microenvironment.
Fig. 4: Intrinsic and extrinsic factors that might contribute to microglial heterogeneity in the tumour microenvironment.
Fig. 5: TAM characteristics might contribute an additional stratum in the classification of primary brain tumours.

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Acknowledgements

The authors’ research is supported by grants from the Swedish Research Council (to B.J.), Swedish Cancer Foundation (to B.J.), Swedish Childhood Cancer Foundation (to K.B.), Swedish Cancer Society (to B.J.), Swedish Brain Foundation (to B.J.), Åke Wiberg Foundation (to M.C.), Petrus och Augusta Hedlund Foundation (to M.C.) and Karolinska Institutet Foundations (to B.J.).

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  1. Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden

    Lily Keane, Mathilde Cheray & Bertrand Joseph

  2. Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden

    Klas Blomgren

  3. Department of Paediatric Oncology, Karolinska University Hospital, Stockholm, Sweden

    Klas Blomgren

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  1. Lily Keane
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  2. Mathilde Cheray
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L.K. and B.J. contributed to all aspects of the article. M.C. and K.B. contributed substantially to discussions of the article content and participated in review and/or editing of the manuscript before submission.

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Correspondence to Bertrand Joseph.

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Keane, L., Cheray, M., Blomgren, K. et al. Multifaceted microglia — key players in primary brain tumour heterogeneity. Nat Rev Neurol 17, 243–259 (2021). https://doi.org/10.1038/s41582-021-00463-2

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