Epigenetic alterations in cancer cells lead to secretion of various cytokines, chemokines, and factors into the TME. Mechanistically, certain epigenetic modulations (e.g., chromatin remodeling and superenhancer formation) can directly regulate cytokine and chemokine expression. In addition, epigenetic alterations (e.g., histone acetylation and m⁶A mRNA modification) promote cytokine expression through indirect mechanisms, in which other pathways (e.g., NOTCH pathway and NF-κB pathway) control the expression of downstream targeted genes. Cancer cell–secreted cytokines bind to specific cytokine receptors on myeloid cells (e.g., macrophages, MDSCs, and neutrophils), promoting their tumor infiltration and immunosuppressive polarization. Consequently, immunosuppressive myeloid cells inhibit the infiltration, activation, and cytotoxic function of T cells, resulting in immune escape. BHLHE41, basic helix-loop-helix family member e41; CCL20, chemokine ligands 20; CECR2, cat eye syndrome chromosome region candidate 2; CHD1, chromodomain helicase DNA binding protein 1; c-Myc, cellular Myc; CREBBP/EP300, CREB-binding protein and E1A-binding protein P300; CSF1, colony-stimulating factor 1; CXCL1/5/8, C-X-C motif chemokine ligand 1/5/8; m⁶A, N⁶-methyladenosine; MDSC, myeloid-derived suppressor cell; METTL3, methyltransferase like 3; PTEN, phosphatase and tensin homolog; YTHDF2, YTH N6-methyladenosine RNA binding protein 2.