| Summary: | The tumor immune microenvironment (TIME), an immunosuppressive niche, plays a pivotal role in contributing to the development, progression, and immune escape of various types of cancer. Compelling evidence highlights the feasibility of cancer therapy targeting the plasticity of TIME as a strategy to retrain the immunosuppressive immune cells, including innate immune cells and T cells. Epigenetic alterations, such as DNA methylation, histone post-translational modifications, and noncoding RNA-mediated regulation, regulate the expression of many human genes and have been reported to be accurate in the reprogramming of TIME according to vast majority of published results. Recently, mounting evidence has shown that the gut microbiome can also influence the colorectal cancer and even extraintestinal tumors via metabolites or microbiota-derived molecules. A tumor is a kind of heterogeneous disease with specificity in time and space, which is not only dependent on genetic regulation, but also regulated by epigenetics. This review summarizes the reprogramming of immune cells by epigenetic modifications in TIME and surveys the recent progress in epigenetic-based cancer clinical therapeutic approaches. We also discuss the ongoing studies and future areas of research that benefits to cancer eradication.
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