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Microenvironmental Clues for Glioma Immunotherapy

  • Neuro-Oncology (LE Abrey, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Gliomas have been viewed for decades as inaccessible for a meaningful antitumor immune response as they grow in a sanctuary site protected from infiltrating immune cells. Moreover, the glioma microenvironment constitutes a hostile environment for an efficient antitumor immune response as glioma-derived factors such as transforming growth factor β and catabolites of the essential amino acid tryptophan paralyze T-cell function. There is growing evidence from preclinical and clinical studies that a meaningful antitumor immunity exists in glioma patients and that it can be activated by vaccination strategies. As a consequence, the concept of glioma immunotherapy appears to be experiencing a renaissance with the first phase 3 randomized immunotherapy trials entering the clinical arena. On the basis of encouraging results from other tumor entities using immunostimulatory approaches by blocking endogenous T-cell suppressive pathways mediated by cytotoxic T-lymphocyte antigen 4 or programmed cell death protein 1/programmed cell death protein 1 ligand 1 with humanized antibodies, there is now a realistic and promising option to combine active immunotherapy with agents blocking the immunosuppressive microenvironment in patients with gliomas to allow a peripheral antitumor immune response induced by vaccination to become effective. Here we review the current clinical and preclinical evidence of antimicroenvironment immunotherapeutic strategies in gliomas.

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Abbreviations

BBB:

Blood–brain-barrier

CNS:

Central nervous system

COX:

Cyclooxygenase

CTLA4:

Cytotoxic T-lymphocyte antigen 4

GIC:

Glioma-initiating cell

IDO:

Indoleamine 2,3-dioxygenase

PD1:

Programmed cell death protein 1

PDL1:

Programmed cell death protein 1 ligand 1

STAT3:

Signal transducer and activator of transcription 3

Treg :

Regulatory T cells

TDO:

Tryptophan 2,3-dioxygenase

TGF-β:

Transforming growth factor β

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Acknowledgments

This work was supported by a grant from German Cancer Aid (110392) to Michael Platten and the German Research Foundation (SFB938 TP K) to Michael Platten and Wolfgang Wick.

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Conflict of Interest

Katharina Ochs, Dieter Lemke, and Christiane Opitz declare that they have no conflict of interest.

Michael Platten is a member of the advisory boards of Merck and Miltenyi Biotech, has received speakers honoraria from Merck, Medac, and Novartis, and has received research funding from Merck, Bayer Schering, and Novartis unrelated to this article.

Wolfgang Wick has received consulting and lecture fees from MSD, Roche, and Magforce, as well as research support from Apogenix, Boehringer Ingelheim, Eli Lilly, MSD, and Roche. He serves on the steering committees of the AVAglio and CENTRIC trials and is the lead investigator of other trials in glioma.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Neurooncology, University Hospital Heidelberg and National Center for Tumor Diseases, German Cancer Consortium (DKTK) Clinical Cooperation Units, Im Neuenheimer Feld, Heidelberg, Germany

    Michael Platten, Katharina Ochs, Dieter Lemke, Christiane Opitz & Wolfgang Wick

  2. CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Michael Platten & Katharina Ochs

  3. CCU Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Dieter Lemke & Wolfgang Wick

  4. Young Investigator Group Brain Cancer Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Christiane Opitz

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  1. Michael Platten
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  2. Katharina Ochs
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  3. Dieter Lemke
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  4. Christiane Opitz
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  5. Wolfgang Wick
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Correspondence to Michael Platten.

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This article is part of the Topical Collection on Neuro-Oncology

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Platten, M., Ochs, K., Lemke, D. et al. Microenvironmental Clues for Glioma Immunotherapy. Curr Neurol Neurosci Rep 14, 440 (2014). https://doi.org/10.1007/s11910-014-0440-1

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