Epigenetic modifiers as new immunomodulatory therapies in solid tumours

Area of Science:

• Oncology
• Immunology
• Epigenetics

Background:

• Immune therapies have improved cancer survival, but resistance remains a challenge.
• Epigenetic modifiers show promise in enhancing patient response to immunotherapies.
• Understanding these interactions is crucial for improving cancer treatment outcomes.

Purpose of the Study:

• To review preclinical and clinical evidence on the immunomodulatory properties of epigenetic agents.
• To explore the therapeutic potential of epigenetic modifiers in cancer treatment.
• To describe experimental approaches, clinical applicability, and ongoing trials.

Main Methods:

• Systematic review of preclinical evidence and clinical studies.
• Analysis of epigenetic agents including HDAC, DNMT, BRD, KDM1, and EZH2 inhibitors.
• Evaluation of their impact on cancer cells, immune cells, and the tumor microenvironment.

Main Results:

• Epigenetic modifiers possess intrinsic immunomodulatory effects.
• These agents can alter cancer cell antigen presentation, induce immunogenic cell death, and modulate cytokine secretion.
• They also impact immune cell lineage, differentiation, activation, and antitumor capabilities, as well as microenvironmental components like Tregs and macrophages.

Conclusions:

• Epigenetic modifiers can significantly enhance tumor immunogenicity and sensitivity to immune agents.
• Combinations with immune checkpoint blockers or adoptive T-cell therapy are promising.
• Optimal trial design and patient selection are essential for developing these combined approaches.