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Brain immunology and immunotherapy in brain tumours

Nature Reviews Cancer volume 20, pages 12–25 (2020)Cite this article

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Abstract

Gliomas, the most common malignant primary brain tumours, remain universally lethal. Yet, seminal discoveries in the past 5 years have clarified the anatomy, genetics and function of the immune system within the central nervous system (CNS) and altered the paradigm for successful immunotherapy. The impact of standard therapies on the response to immunotherapy is now better understood, as well. This new knowledge has implications for a broad range of tumours that develop within the CNS. Nevertheless, the requirements for successful therapy remain effective delivery and target specificity, while the dramatic heterogeneity of malignant gliomas at the genetic and immunological levels remains a profound challenge.

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Fig. 1: Immune privilege in the brain.
Fig. 2: Immunosuppressive mediators and therapeutic targets in the brain tumour microenvironment.
Fig. 3: Epigenetic events play a key role in modulating immune responses to brain tumours.
Fig. 4: Chimeric antigen receptor T cell immunotherapy in brain tumours.

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Acknowledgements

This work was supported by grants from the National Institutes of Health to J.H.S.: R01-NS099463, P50-CA190991, P30-CA14236, P01-CA225622, R01-CA235612, U01-NS090284, R01-NS085412 and R01-CA175517. The funders had no role in the preparation of the manuscript or the decision to publish. The authors acknowledge T. Wright for her assistance with manuscript preparation.

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Authors and Affiliations

  1. The Preston Robert Tisch Brain Tumor Center at Duke, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA

    John H. Sampson, Peter E. Fecci & David M. Ashley

  2. Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA

    John H. Sampson & Peter E. Fecci

  3. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Michael D. Gunn

  4. Duke Center for Brain and Spine Metastasis, Duke University Medical Center, Durham, NC, USA

    Peter E. Fecci

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All authors provided substantial contributions to the discussions of the content, made significant contributions to the writing of the article and contributed equally to the review and editing of the manuscript before submission.

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Correspondence to John H. Sampson.

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Competing interests

J.H.S. has an equity interest in Annias Immunotherapeutics, which has licensed intellectual property from Duke related to the use of the PEP-CMV vaccine in the treatment of glioblastoma. J.H.S. has an equity interest in Istari Oncology, which has licensed intellectual property from Duke related to the use of polio virus and D2C7 in the treatment of glioblastoma. J.H.S. has additional relationships with Celldex (intellectual property, royalties) and Medicenna Therapeutics (consulting). J.H.S. is an inventor on patents related to the PEP-CMV DC vaccine with tetanus, as well as to polio virus vaccine and D2C7 in the treatment of glioblastoma. D.M.A is an inventor on patents related to the use of polio virus. M.D.G is an inventor on patents related to cellular vaccines. Duke and certain Duke investigators could benefit financially if related therapies prove effective and are commercially successful. P.E.F. has no relevant disclosures.

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Glossary

Tumour-treating fields

(TTFields). External application of alternating electrical fields to disrupt the multiplication of tumour cells.

Glial–lymphatic (glymphatic) pathway

A recently characterized functional waste clearance pathway in the central nervous system that connects the brain interstitium to the cerebrospinal fluid spaces via aquaporin channels.

Glia limitans

A thin barrier of astrocyte foot processes associated with the parenchymal basal lamina surrounding the brain and spinal cord. The glia limitans plays a crucial role in regulating the movement of small molecules and cells into the brain parenchyma.

Microglia

The resident self-renewing population of macrophages in the central nervous system.

Lynch syndrome

Also known as hereditary non-polyposis colorectal cancer. A type of inherited cancer syndrome associated with a genetic predisposition to different cancer types, including glioblastoma.

Myelosuppression

A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells and platelets.

Lymphopenia

The condition of having an abnormally low level of lymphocytes in the blood.

Lymphokine-activated killer (LAK) cells

Lymphocytes cultured in the presence of interleukin-2 (IL-2) to stimulate their cytotoxic activity.

Pseudoprogression

A new or enlarging area of contrast agent enhancement occurring early after the end of radiotherapy or immunotherapy (for example, within 3–4 months), in the absence of true tumour growth, that subsides or stabilizes without a change in therapy.

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Sampson, J.H., Gunn, M.D., Fecci, P.E. et al. Brain immunology and immunotherapy in brain tumours. Nat Rev Cancer 20, 12–25 (2020). https://doi.org/10.1038/s41568-019-0224-7

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