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Yelton et al. Neuroimmunol Neuroinflammation 2018;5:46 Neuroimmunology and
DOI: 10.20517/2347-8659.2018.58 Neuroinflammation

Review Open Access

Histone deacetylase enzymes and selective histone
deacetylase inhibitors for antitumor effects and
enhancement of antitumor immunity in glioblastoma

Caleb J. Yelton, Swapan K. Ray

Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA.

Correspondence to: Dr. Swapan K. Ray, Department of Pathology, Microbiology, and Immunology, University of South Carolina School
of Medicine, Building 2, Room C11, 6439 Garners Ferry Road, Columbia, SC 29209, USA. E-mail: swapan.ray@uscmed.sc.edu
How to cite this article: Yelton CJ, Ray SK. Histone deacetylase enzymes and selective histone deacetylase inhibitors for antitumor
effects and enhancement of antitumor immunity in glioblastoma. Neuroimmunol Neuroinflammation 2018;5:46.
http://dx.doi.org/10.20517/2347-8659.2018.58
Received: 15 Sep 2018 First Decision: 8 Oct 2018 Revised: 28 Oct 2018 Accepted: 28 Oct 2018 Published: 12 Nov 2018

Science Editor: Athanassios P. Kyritsis Copy Editor: Cui Yu Production Editor: Zhong-Yu Guo

Abstract
Glioblastoma multiforme (GBM), which is the most common primary central nervous system malignancy in adults,
has long presented a formidable challenge to researchers and clinicians alike. Dismal 5-year survival rates of the
patients with these tumors and the ability of the recurrent tumors to evade primary treatment strategies have
prompted a need for alternative therapies in the treatment of GBM. Histone deacetylase (HDAC) inhibitors are
currently a potential epigenetic therapy modality under investigation for use in GBM with mixed results. While
these agents show promise through a variety of proposed mechanisms in the pre-clinical realm, only several of
these agents have shown this same promise when translated into the clinical arena, either as monotherapy or for
use in combination regimens. This review will examine the current state of use of HDAC inhibitors in GBM, the
mechanistic rationale for use of HDAC inhibitors in GBM, and then examine an exciting new mechanistic revelation
of certain HDAC inhibitors that promote antitumor immunity in GBM. The details of this antitumor immunity will be
discussed with an emphasis on application of this antitumor immunity towards developing alternative therapies for
treatment of GBM. The final section of this article will provide an overview of the current state of immunotherapy
targeted specifically to GBM.

Keywords: Glioblastoma, histone deacetylase inhibitors, antitumor effects, antitumor immunity

INTRODUCTION
Glioblastoma multiforme (GBM) is the most prevalent primary malignancy in the central nervous system
(CNS) in adults. GBM still remains incurable and thus continues to present a formidable challenge to both

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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