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

作     者：Caleb J.Yelton Swapan K.Ray 

作者机构：Department of PathologyMicrobiologyand ImmunologyUniversity of South Carolina School of MedicineColumbiaSC 29209USA 

出 版 物：《Neuroimmunology and Neuroinflammation》 (神经免疫与神经炎症（英文版）)

年 卷 期：2018年第5卷第11期

页      面：1-18页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：The work was supported in part by an award from the Soy Health Research Program an investigator-initiated research grant (SCIRF-2015-I-01) from South Carolina Spinal Cord Injury Research Fund earlier R01 grants (CA-091460, and NS-057811) from the National Institutes of Health 

主　　题：Glioblastoma histone deacetylase inhibitors antitumor effects antitumor immunity 

摘      要：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.