Epigenetic Regulation of Cancer Immune Cells
Introduction
The epigenetic regulation of the anti-tumor immune responses has multiple components that governs regulation of gene expression in many cells involved in the process. Epigenetic regulations such as the role of DNA methylation, organization of nucleosomes, modifications of histones, and expression of transcription factors in the development and maintenance of a dysfunctional anti-tumor immunity has been the focus of intense research - primarily in models for chronic viral infections but also in murine models for cancers. It is important to highlight the difficulties of reaching definitive conclusions in the epigenetic regulation of anti-tumor immunity partly related to the lack of accurate preclinical models that mimic the clinic tumor development in humans. The role of epigenetic regulation of the immune response in cancer has been studied primarily in T cells, Natural Killer cells and macrophages.
Section snippets
Cytotoxic CD8+ T cells
T cell differentiation is associated with the acquisition of different epigenetic or chromatin states [1,2]. Differentiation from a naïve to active and a memory phenotype is marked by epigenetic modifications in the promoter or regulatory regions of relevant gene loci in models of chronic viral infections [3]. Although there are many similarities between the immune response in chronic viral infections and the anti-tumor response, the mechanisms and epigenetic imprinting of tumor-induced immune
Natural Killer Cells
Natural killer (NK) cells are innate lymphocytes, important in immune surveillance. Tumor evasion of NK cells has been linked to multiple mechanisms, including the expression of inhibitory factors (HLA-E, HLA-G) [36] by releasing inhibitory cytokines (IL-10, transforming growth factor β (TGF-β), prostaglandin E2) [[37], [38], [39]], and expression of checkpoint inhibitor ligands (PD-L1, TIM-3, LAG3) [[40], [41], [42]]. Epigenetic mechanisms, including DNA and histone methylation, have been
Future directions
Identification of different subsets such as effector, memory and exhausted T cells with the help of single cell RNA sequencing enables deeper understanding of genes and transcription factors that are involved in generating dysfunctional anti-tumor immune system. Additionally, knowledge on pathways that mediate anti-tumor immunity may be obtained. The expression and function of some epigenetic regulators mentioned above have been confirmed in humans; however, there is evidence that the
Funding
This study was supported by a Mizzou Advantage Interdisciplinary Research Grant (MAIRG) (D.A.P., G.L., and J.T.K). J.B.M. received funding from the Department of Veteran’s AffairsK2BX004346-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans’ Affairs. The funding bodies had no role in study design, collection, analysis, interpretation of data or writing the manuscript.
Declaration of Competing Interest
The authors report no declarations of interest.
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