Page 401 - Read Online

Pearce et al. Neuroimmunol Neuroinflammation 2018;5:47 I http://dx.doi.org/10.20517/2347-8659.2018.46 Page 13 of 16

While DC vaccines have shown their ability to prolong OS, correlation of immune response with long-
term outcomes remains unclear, and prognostic markers for determining patients that will best respond
to DC vaccines needs to be further elucidated. DC vaccines targeting specific proteins, the multi-epitope
trial and cytomegalovirus trial, show great clinical potential, but must be evaluated on a larger scale before
conclusions can be drawn. Whole-tumor lysate vaccines are the most advanced in terms of clinical trial
progress and demonstrate clear improvements, with 25% of patients achieving above a three-year survival
rate in the largest phase 3 trial to date. This trial further demonstrated increased efficacy in patients with
methylated O6-methylguanine-DNA methyltransferase, offering another potential prognostic marker for
[89]
identifying patients who might best respond to autologous tumor-lysate DC vaccines . For patients whose
tumors can be biopsied, DC vaccines offer a significant improvement in survival outcome, which will be
enhanced as prognostic markers become clearer.

CONCLUSION
Glioma-targeted immunotherapy is still in its infancy. Although ACT, NK cells, checkpoint inhibitors and
vaccines have proven their efficacy in other cancers, a deeper understanding of the features specific to solid
gliomas is necessary for refined therapy adjustment. Furthermore, improved human preclinical models can
more accurately illustrate the human CNS microenvironment and immune cell relationships with the BBB.
Studies utilizing these models can deepen our understanding of immune function, ultimately revealing
ways to enhance combined treatment modalities. Yet as these ambiguities are made clear, the future of these
treatments against GBM remains bright. These methods of tumor eradication address limitations posed by
conventional surgical, radiation, and chemotherapies.

DECLARATIONS
Authors’ contributions
Conceptualize the project, write and edit the manuscript: Low WC, Crane AT, Pearce CM, Chrostek MR
Write various sections of the manuscript: Fellows EG, Toman NG, Tran S

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported in part by funds from Suzanne M. Schwarz.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2018.

REFERENCES
1. Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee ShU. Glioblastoma multiforme: a review of its epidemiology and pathogenesis
through clinical presentation and treatment. Asian Pac J Cancer Prev 2017;18:3-9.
2. Parker NR, Hudson AL, Khong P, Parkinson JF, Dwight T, et al. Intratumoral heterogeneity identified at the epigenetic, genetic and
transcriptional level in glioblastoma. Sci Rep 2016;6:22477.