Epigenetic modifiers synergize with immune-checkpoint blockade to enhance long-lasting antitumor efficacy

Area of Science:

• Oncology
• Immunology
• Epigenetics

Background:

• Immune-checkpoint inhibitors (ICIs) are crucial cancer therapies, but response rates are limited.
• Novel therapeutic combinations are needed to improve ICI efficacy.
• Histone deacetylases (HDACs) are emerging targets for cancer immune modulation.

Purpose of the Study:

• To investigate the efficacy of combining the HDAC inhibitor entinostat with anti-PD-1 therapy in a bladder cancer model.
• To elucidate the underlying mechanisms of synergy between HDAC inhibition and ICI therapy.

Main Methods:

• Utilized a preclinical bladder cancer model.
• Administered entinostat in combination with anti-PD-1 therapy.
• Assessed tumor immune phenotype, antitumor efficacy, and neoantigen presentation.

Main Results:

• The combination therapy demonstrated substantial antitumor efficacy.
• Entinostat promoted a T cell-inflamed tumor microenvironment.
• HDAC inhibition enhanced tumor neoantigen presentation, leading to immune editing of tumor antigens.

Conclusions:

• Epigenetic modifiers like entinostat can synergize with immune-checkpoint blockade.
• This combination strategy offers a promising approach for enhanced and durable antitumor activity.
• The findings highlight a mechanism for improving cancer immunotherapy response rates.