Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Immune checkpoint inhibitors (ICIs) targeting receptors like PD-1 and CTLA-4 are vital in cancer immunotherapy.
• Malignancies employ immune evasion strategies, limiting the efficacy of single-agent immunotherapies.
• Combining epigenetic modulators with immunotherapeutics offers a strategy to overcome these limitations.

Purpose of the Study:

• To review current strategies for enhancing immunotherapy responses.
• To elucidate the immune-modulating effects of histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi).
• To highlight the advantages of combinatorial therapy over single-drug treatments in cancer.

Main Methods:

• Review of preclinical data from mouse models on co-treatment with HDACi or DNMTi and immunotherapeutics.
• Analysis of in vitro and in vivo studies demonstrating improved outcomes with combined therapies.
• Examination of clinical trial data on the efficacy of HDACi and DNMTi in augmenting anti-PD-1 immunotherapy response.

Main Results:

• Preclinical studies confirm the feasibility and effectiveness of combining epigenetic modulators with immunotherapeutics.
• Co-treatment with pan- or class I-selective HDACi or DNMTi improved outcomes in various cancer models.
• Clinical trials indicate that HDACi and DNMTi significantly enhance responses to anti-PD-1 immunotherapy across different tumor types.

Conclusions:

• Epigenetic modulators like HDACi and DNMTi play a crucial role in immune modulation.
• Combination therapy involving epigenetic modulators and immunotherapeutics demonstrates superior efficacy compared to single-agent treatments.
• This combinatorial approach holds significant potential for improving cancer treatment outcomes by overcoming tumor immune evasion.