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Cellular and Molecular Biology

IL-10 in glioma

Abstract

The prognosis for patients with glioblastoma (GBM), the most common and malignant type of primary brain tumour, is very poor, despite current standard treatments such as surgery, radiotherapy and chemotherapy. Moreover, the immunosuppressive tumour microenvironment hinders the development of effective immunotherapies for GBM. Cytokines such as interleukin-10 (IL-10) play a major role in modulating the activity of infiltrating immune cells and tumour cells in GBM, predominantly conferring an immunosuppressive action; however, in some circumstances, IL-10 can have an immunostimulatory effect. Elucidating the function of IL-10 in GBM is necessary to better strategise and improve the efficacy of immunotherapy. This review discusses the immunostimulatory and immunosuppressive roles of IL-10 in the GBM tumour microenvironment while considering IL-10-targeted treatment strategies. The molecular mechanisms that underlie the expression of IL-10 in various cell types are also outlined, and how this resulting information might provide an avenue for the improvement of immunotherapy in GBM is explored.

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Fig. 1: Elevated levels of IL10, and IL-10 receptors, IL10RA and IL10RB mRNA, in glioma patient samples.
Fig. 2: IL-10-mediated TAM activation leads to an anti-inflammatory state.
Fig. 3: Diverse roles of IL-10 in the glioma TME.

Data availability

Results generated in Fig. 1 used gene expression data generated by the TCGA Research Network: (https://www.cancer.gov/tcga) and the Chinese Glioma Genome Atlas: (http://www.cgga.org.cn/).

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Acknowledgements

We thank the members of the Brain Cancer Biology Laboratory for proof-reading the manuscript.

Funding

This work was funded by the National Health & Medical Research Council MRFF Accelerated Research (APP1158175), Australian Brain Cancer Mission, Cancer Australia (to S.S.S.), the Department of Surgery Seed Funding, the Department of Microbiology and Immunology, The University of Melbourne, the CASS Foundation and the Brain Foundation Australia.

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All authors made a substantial contribution to all aspects of the preparation of this paper, including conceiving the work that led to the submission, drafting, and revising the paper and approving the final version. First authorship is shared by S.S.W. and M.D.

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Correspondence to Theo Mantamadiotis.

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Widodo, S.S., Dinevska, M., Furst, L.M. et al. IL-10 in glioma. Br J Cancer 125, 1466–1476 (2021). https://doi.org/10.1038/s41416-021-01515-6

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