Abstract
Simple SummaryEpigenetic mechanisms including methylation play an essential role in regulating gene expression not only in cancer cells but also in immune cells. Although role of DNA methylation has been extensively studied in tumor cells in tumor microenvironment (TME), the understanding of transcriptional regulation of pro- and anti-cancer immune cells in TME is beginning to unfold. This review focuses on the role of DNA and RNA methylation in regulating immune responses in innate and adaptive immune cells during their activation, differentiation, and function phase in cancer and in non-cancer pathologies. Uncovering these crucial regulatory mechanisms can trigger discovery of novel therapeutic targets which could enhance immunity against cancer to decrease cancer associated morbidity and mortality.DNA and RNA methylation play a vital role in the transcriptional regulation of various cell types including the differentiation and function of immune cells involved in pro- and anti-cancer immunity. Interactions of tumor and immune cells in the tumor microenvironment (TME) are complex. TME shapes the fate of tumors by modulating the dynamic DNA (and RNA) methylation patterns of these immune cells to alter their differentiation into pro-cancer (e.g., regulatory T cells) or anti-cancer (e.g., CD8+ T cells) cell types. This review considers the role of DNA and RNA methylation in myeloid and lymphoid cells in the activation, differentiation, and function that control the innate and adaptive immune responses in cancer and non-cancer contexts. Understanding the complex transcriptional regulation modulating differentiation and function of immune cells can help identify and validate therapeutic targets aimed at targeting DNA and RNA methylation to reduce cancer-associated morbidity and mortality.
Highlights
Epigenetic modifications are heritable changes regulating the cellular gene expression patterns required for the normal development and maintenance of various tissue functions [1,2,3]
The role of DNA and RNA methylation in regulating the differentiation and activity of immune cells within the tumor microenvironment (TME) is key to determining the fate of tumor growth or suppression (Figure 5)
A pro-cancer TME has immune cells expressing pro-tumor cytokines that lead to tumor growth and progression, whereas the reverse is seen in the anti-cancer TME
Summary
Epigenetic modifications are heritable changes regulating the cellular gene expression patterns required for the normal development and maintenance of various tissue functions [1,2,3]. Whereas genetic mutations result in the activation/inactivation of certain genes playing a pivotal role in carcinogenesis, abnormalities in the epigenetic landscape can lead to altered gene expression and function, genomic instability, and malignant cellular transformation (Figure 1) [3,4]. The three most studied epigenetic mechanisms that result in cancer are alterations in DNA methylation, histone modification, and non-coding RNA (ncRNA) expression.
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