Figure 1.

An overview of epigenetic mechanisms governing cellular processes and the drugs targeting respective epigenetic processes. There are two possible states of chromatin organization: (A) the “closed” chromatin associated with heterochromatin formation and transcriptional repression drives gene silencing. (B) The mechanistic organization of euchromatin maintains the “open” chromatin confirmation and allows active gene expression. (C) Examples of how epigenetic drugs modulate the γδ T-cell/Treg/tumor interaction. In the circle (left part), the epigenetic drugs (on the right-hand side) that are either in pre-clinical development or clinically approved are listed along with the respective target proteins (on the left-hand side). These are the key proteins for diverse epigenetic processes. The effect of the listed epigenetic drugs on immune cells (γδ T cells and Treg) and tumor cells are shown in the rectangles (right part). As marked by asterisk (*), the epigenetic drugs are proposed to synergize, leading to increased efficacy of γδ T cell-based immunotherapy. HDAC, histone deacetylase; HP1, heterochromatin protein 1; MeCP2, methyl-CpG binding protein 2; HAT, histone acetyltransferase; BET, Bromodomain and ExtraTerminal; TF, transcription factor; TAF, transcription-associated factors; RNA polII, RNA polymerase II; TET, ten-eleven translocation; VPA, valproic acid; NKG2D, natural-killer group 2, member D receptor protein; NKG2DL, ligands for NKG2D receptor protein; PD-L1, programmed death ligand 1; FoxP3, forkhead Box P3; Treg, regulatory T cells.