Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth

Area of Science:

• Immunology
• Oncology
• Epigenetics

Background:

• Major histocompatibility complex (MHC) class II pathway protein expression in ovarian cancer is linked to improved patient survival.
• Epigenetic alterations play a role in ovarian cancer progression and immune evasion.

Purpose of the Study:

• To investigate the effect of epigenetic modulators on MHC class II pathway expression in ovarian cancer.
• To evaluate the impact of these epigenetic treatments on ovarian tumor growth in preclinical models.

Main Methods:

• Murine and human ovarian cancer cells were treated with histone deacetylase inhibitors (e.g., entinostat) and a DNA methyltransferase inhibitor (e.g., azacytidine).
• Messenger RNA (mRNA) and protein expression of MHC class II pathway components were assessed using quantitative polymerase chain reaction (qPCR) and flow cytometry.
• Tumor growth was evaluated in patient-derived xenografts and in immune-competent mice bearing ID8 ovarian tumors.

Main Results:

• Entinostat and azacytidine treatment increased mRNA and protein expression of MHC II pathway components (CD74, CIITA, H2-Aa, H2-Eb1) in vitro.
• Combination epigenetic therapy demonstrated enhanced MHC II protein expression compared to single-agent treatments.
• Combination treatment significantly increased MHC II pathway mRNA transcripts in patient-derived xenografts and MHC II expression on tumors in mice.
• Combined epigenetic treatment significantly reduced ID8 ovarian tumor growth in immune-competent mice.

Conclusions:

• Epigenetic modulation with entinostat and azacytidine effectively upregulates MHC class II expression on ovarian cancer cells.
• This epigenetic strategy demonstrates potential for impeding ovarian tumor growth.
• The findings support further investigation of epigenetic therapy targeting the MHC class II pathway in ovarian cancer patients.