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Oncotarget. 2017 Jul 4;8(27):44159-44170. doi: 10.18632/oncotarget.17395.

Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth.

Author information

1
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA.
2
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
3
Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
4
NIH Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL, USA.
5
Department of Medicine, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama, USA.
6
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.

Abstract

Expression of MHC class II pathway proteins in ovarian cancer correlates with prolonged survival. Murine and human ovarian cancer cells were treated with epigenetic modulators - histone deacetylase inhibitors and a DNA methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway were evaluated by qPCR and flow cytometry. Treatment with entinostat and azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2-Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment with either agent. A dose dependent response in mRNA and protein expression was seen with entinostat. Combination treatment showed higher MHC II protein expression than with single agent treatment. In patient derived xenografts, CIITA, CD74, and MHC II mRNA transcripts were significantly increased after combination treatment. Expression of MHC II on ovarian tumors in MISIIR-Tag mice was increased with both agents relative to control. Combination treatment significantly reduced ID8 tumor growth in immune-competent mice. Epigenetic treatment increases expression of MHC II on ovarian cancer cells and impedes tumor growth. This approach warrants further study in ovarian cancer patients.

KEYWORDS:

DNMTi; HDACi; MHC II; epigenetics; ovarian cancer

PMID:
28498806
PMCID:
PMC5546470
DOI:
10.18632/oncotarget.17395
[Indexed for MEDLINE]
Free PMC Article

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