Harnessing Epigenetic Mechanisms to Overcome Immune Evasion in Cancer: The Current Strategies and Future Directions

Combining epigenetic alterations with cancer immunotherapy offers a promising approach to improve therapeutic outcomes by targeting the complex biology of tumors. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) play a dual role in maintaining immune homeostasis and promoting cancer progression. Changes like hypomethylation in tumor cells can contribute to immune evasion and treatment resistance. Advances in epigenetic tools, particularly clustered regularly interspaced short palindromic repeat (CRISPR) and their associated protein (Cas9)-based epigenetic editing, allow for precise gene expression control, opening new avenues for research and therapy. The improved accuracy of CRISPR/dCas9 systems, when paired with appropriate delivery methods such as viral vectors or nanoparticles, has facilitated innovative combination therapies involving immune checkpoint inhibitors and epigenetic drugs. These combinations enhance the immune system's ability to recognize and destroy cancer cells. Despite these advancements, challenges like off-target effects, delivery issues, and resistance remain. Current research is focused on identifying new therapeutic targets, improving delivery systems, and using real-time feedback to refine treatment. Overall, combining immunotherapy with epigenetic modifications holds significant potential for personalized cancer treatment, paving the way for more effective and individualized therapeutic strategies that target both the immune system and the tumor microenvironment. Further development in this area is expected to revolutionize cancer therapy and improve patient outcomes.