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T-Cell based therapies for overcoming neuroanatomical and immunosuppressive challenges within the glioma microenvironment

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Abstract

Glioblastoma remains as the most common and aggressive primary adult brain tumor to date. Within the last decade, cancer immunotherapy surfaced as a broadly successful therapeutic approach for a variety of cancers. However, due to the neuroanatomical and immunosuppressive nature of malignant gliomas, conventional chemotherapy and radiotherapy treatments garner limited efficacy in patients with these tumors. The intricate structure of the blood brain barrier restricts immune accessibility into the tumor microenvironment, and malignant gliomas can activate various adaptive responses to subvert anticancer immune responses and reinstate an immunosuppressive milieu. Yet, evidence of lymphocyte infiltration within the brain and recent advancements made in cell engineering technologies implicate the vast potential in the future of neuro-oncological immunotherapy. Previous immunotherapy platforms have paved way to improved modalities, which includes but is not limited to personalized vaccines and chimeric antigen receptor T-cell therapy. This review will cover the various neuroanatomical and immunosuppressive features of central nervous system tumors and highlight the innovations made in T-cell based therapies to overcome the challenges presented by the glioblastoma microenvironment.

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Funding

Funding was provided by National Institute of Neurological Disorders and Stroke (Grant No. 1R35 NS105068).

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  1. Department of Neurological Surgery, University of California, San Francisco, Helen Diller Family Cancer Research Building HD 472 1450 3rd Street, San Francisco, CA, 94158-0520, USA

    Darwin Kwok & Hideho Okada

  2. The Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA

    Hideho Okada

  3. Cancer Immunotherapy Program, University of California, San Francisco, CA, USA

    Hideho Okada

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  1. Darwin Kwok
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Kwok, D., Okada, H. T-Cell based therapies for overcoming neuroanatomical and immunosuppressive challenges within the glioma microenvironment. J Neurooncol 147, 281–295 (2020). https://doi.org/10.1007/s11060-020-03450-7

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