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The role of microglia and macrophages in glioma maintenance and progression

Nature Neuroscience volume 19, pages 20–27 (2016)Cite this article

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Abstract

There is a growing recognition that gliomas are complex tumors composed of neoplastic and non-neoplastic cells, which each individually contribute to cancer formation, progression and response to treatment. The majority of the non-neoplastic cells are tumor-associated macrophages (TAMs), either of peripheral origin or representing brain-intrinsic microglia, that create a supportive stroma for neoplastic cell expansion and invasion. TAMs are recruited to the glioma environment, have immune functions, and can release a wide array of growth factors and cytokines in response to those factors produced by cancer cells. In this manner, TAMs facilitate tumor proliferation, survival and migration. Through such iterative interactions, a unique tumor ecosystem is established, which offers new opportunities for therapeutic targeting.

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Figure 1: Microglia and monocytes have distinct cellular origins.
Figure 2: Microglia and monocytes converge in high-grade glioma (HGG).
Figure 3: M1/M2 profile of TMAs.
Figure 4: Glioma cells release several factors, which attract TAMs to the tumor tissue.
Figure 5: TAM glioma crosstalk.
Figure 6: Illustration of the complexity and cellular composition of glioma.

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Acknowledgements

The authors would like to thank D. Schumick for his great work with illustrations. This work was supported by the Deutsche Forschungsgemeinschaft (TR 43, KE 329/30-1; H.K.) and Neurocure (H.K.) as well as funding from the Department of Defense (W81XWH-13-1-0094, D.H.G.) and James S. McDonnell Foundation (D.H.G.) and a collaborative U01 grant from the National Cancer Institute (U01-CA160882; D.H., D.H.G. and H.K.).

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  1. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA

    Dolores Hambardzumyan

  2. Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA

    David H Gutmann

  3. Max Delbrück Center for Molecular Medicine, Berlin, Germany

    Helmut Kettenmann

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D.H., D.H.G. and H.K. wrote and edited the manuscript.

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Correspondence to Helmut Kettenmann.

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Hambardzumyan, D., Gutmann, D. & Kettenmann, H. The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci 19, 20–27 (2016). https://doi.org/10.1038/nn.4185

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