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Table 3 Epigenetic regulation of key molecules in immune and cancer cells

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

[185,186,187]

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.

[167, 169]

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

[190,191,192]