Many epigenetic modifications occur in glioma, in particular the histone-deacetylase class proteins play a pivotal role in glioma development, driving the proliferation rate and the invasiveness of tumor cells, and modulating the tumor microenvironment. In this study, we evaluated the role of the histone deacetylase HDAC8 in the regulation of the immune response in glioma and tumor growth. We found that inhibition of HDAC8 by the specific inhibitor PCI-34051 reduces tumor volume in glioma mouse models. We reported that HDAC8 modulates the viability and the migration of human and murine glioma cells. Interestingly, HDAC8 inhibition increases the acetylation of alpha-tubulin, suggesting this epigenetic modification controls glioma migration. Furthermore, we identify HDAC8 as a key molecule that supports a poorly immunogenic tumor microenvironment, modulating microglial phenotype and regulating the gene transcription of NKG2D ligands that trigger the Natural Killer cell-mediated cytotoxicity of tumor cells. Altogether, these results identify HDAC8 as a key actor in glioma growth and tumor microenvironment, and pave the way to a better knowledge of the molecular mechanisms of immune escape in glioma.

Histone-deacetylase 8 drives the immune response and the growth of glioma / Mormino, Alessandro; Cocozza, Germana; Fontemaggi, Giulia; Valente, Sergio; Esposito, Vincenzo; Santoro, Antonio; Bernardini, Giovanni; Santoni, Angela; Fazi, Francesco; Mai, Antonello; Limatola, Cristina; Garofalo, Stefano. - In: GLIA. - ISSN 0894-1491. - (2021), pp. 1-17. [10.1002/glia.24065]

Histone-deacetylase 8 drives the immune response and the growth of glioma

Alessandro Mormino
Conceptualization
;
Germana Cocozza
Methodology
;
Sergio Valente
Methodology
;
Vincenzo Esposito
Methodology
;
Antonio Santoro
Methodology
;
Giovanni Bernardini
Data Curation
;
Angela Santoni
Investigation
;
Francesco Fazi
Data Curation
;
Antonello Mai
Conceptualization
;
Cristina Limatola
Funding Acquisition
;
Stefano Garofalo
Writing – Original Draft Preparation
2021

Abstract

Many epigenetic modifications occur in glioma, in particular the histone-deacetylase class proteins play a pivotal role in glioma development, driving the proliferation rate and the invasiveness of tumor cells, and modulating the tumor microenvironment. In this study, we evaluated the role of the histone deacetylase HDAC8 in the regulation of the immune response in glioma and tumor growth. We found that inhibition of HDAC8 by the specific inhibitor PCI-34051 reduces tumor volume in glioma mouse models. We reported that HDAC8 modulates the viability and the migration of human and murine glioma cells. Interestingly, HDAC8 inhibition increases the acetylation of alpha-tubulin, suggesting this epigenetic modification controls glioma migration. Furthermore, we identify HDAC8 as a key molecule that supports a poorly immunogenic tumor microenvironment, modulating microglial phenotype and regulating the gene transcription of NKG2D ligands that trigger the Natural Killer cell-mediated cytotoxicity of tumor cells. Altogether, these results identify HDAC8 as a key actor in glioma growth and tumor microenvironment, and pave the way to a better knowledge of the molecular mechanisms of immune escape in glioma.
2021
hdac8; epigenetic; glioma; histone-deacetylase 8 protein; microglia; natural killer cell; natural killer group 2D (NKG2D) ligands; PCI-34051
01 Pubblicazione su rivista::01a Articolo in rivista
Histone-deacetylase 8 drives the immune response and the growth of glioma / Mormino, Alessandro; Cocozza, Germana; Fontemaggi, Giulia; Valente, Sergio; Esposito, Vincenzo; Santoro, Antonio; Bernardini, Giovanni; Santoni, Angela; Fazi, Francesco; Mai, Antonello; Limatola, Cristina; Garofalo, Stefano. - In: GLIA. - ISSN 0894-1491. - (2021), pp. 1-17. [10.1002/glia.24065]
File allegati a questo prodotto
File Dimensione Formato  
Mormino_Histone-deacetylase_2021.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 5.06 MB
Formato Adobe PDF
5.06 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1564224
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 12
social impact