From: Epigenetic modulation of antitumor immunity for improved cancer immunotherapy
Molecule | Cell types | Epigenetic regulation | Reference |
---|---|---|---|
Granzyme B | CD8+ T cells | H3K9Ac at the promoter increased ~ 100-fold within 12 h stimulation | [184] |
IFN-γ | CD8+ T cells (naïve and memory) | Promoter DNA methylation downregulates transcription in naïve cells, while demethylation happens rapidly in memory cells leading to IFN-γ expression | [177] |
IL-2 | CD8+ T cells | 1. The promoter-enhancer region is demethylated following T cell activation. 2.Activated Ag-specific CD8+ T cells exhibit rapid DNA demethylation at the I-2 locus and is maintained through memory development | |
IL-12 | T, NK and macrophages | H3K4me3 up-, H3K27me2 down-regulate IL12p35 and IL12p40 promoters. | [188] |
FoxP3 | Treg | DNA methylation of the CpG island in the enhancer region dictates its expression in T cell subsets. | |
STING | Cancer cells | Promoter hypermethylation of cGAS and STING genes mediated their coordinate transcriptional silencing, and DNA methylation inhibitor can restore their expression. | [189] |
PD-1, CTLA-4, TIM-3, LAG-3, TIGIT and PD-L1 | Cancer and stromal cells | DNA methylation and H4K9 and H3K27 trimethylation are associated with silenced status |