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The immune landscape of common CNS malignancies: implications for immunotherapy

Nature Reviews Clinical Oncology volume 18, pages 729–744 (2021)Cite this article

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Abstract

Immunotherapy has enabled remarkable therapeutic responses across cancers of various lineages, albeit with some notable exceptions such as glioblastoma. Several previous misconceptions, which have impaired progress in the past, including the presence and role of the blood–brain barrier and a lack of lymphatic drainage, have been refuted. Nonetheless, a subset of patients with brain metastases but, paradoxically, not the vast majority of those with gliomas are able to respond to immune-checkpoint inhibitors. Immune profiling of samples obtained from patients with central nervous system malignancies using techniques such as mass cytometry and single-cell sequencing along with experimental data from genetically engineered mouse models have revealed fundamental differences in immune composition and immunobiology that not only explain the differences in responsiveness to these agents but also lay the foundations for immunotherapeutic strategies that are applicable to gliomas. Herein, we review the emerging data on the differences in immune cell composition, function and interactions within central nervous system tumours and provide guidance on the development of novel immunotherapies for these historically difficult-to-treat cancers.

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Fig. 1: Analysis of immune cell populations in various anatomical locations within glioblastomas.
Fig. 2: Analysis of chemokine expression in various anatomical locations within glioblastomas.
Fig. 3: Frequencies of the major immune cell populations and potential immunotherapeutic targets in gliomas and brain metastases.
Fig. 4: Competing transcription factors regulate the activation of innate immune cells.

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Acknowledgements

This research was supported by the National Institutes of Health RO1CA120813, R01NS120547 and P30 CA016672, the Ben and Catherine Ivy Foundation, the MD Anderson GBM Moonshot, the Traver Walsh Foundation, and the Brockman Foundation.

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Authors and Affiliations

  1. Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Martina Ott

  2. Departments of Neurosurgery and Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Robert M. Prins

  3. Department of Neurosurgery, Northwestern University, Chicago, IL, USA

    Amy B. Heimberger

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  1. Martina Ott
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  2. Robert M. Prins
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  3. Amy B. Heimberger
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All authors contributed to all aspects of the preparation of this manuscript.

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Correspondence to Amy B. Heimberger.

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Competing Interests

A.B.H. has acted as a consultant of Caris Life Science and WCG Oncology, has received research funding from Celularity, Carthera and Codiak Bioscience, is the co-owner of patents or other intellectual property, receives or might receive royalties from Celldex Therapeutics, DNAtrix and Moleculin, and holds stock and other ownership interests in Caris Life Science. M.O. and R.M.P. declare no competing interests.

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Ott, M., Prins, R.M. & Heimberger, A.B. The immune landscape of common CNS malignancies: implications for immunotherapy. Nat Rev Clin Oncol 18, 729–744 (2021). https://doi.org/10.1038/s41571-021-00518-9

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