Fig. 3

Epigenetic modulation and tumor immune efficacy. DNMT1 and EZH2 play critical roles in DNA and histone methylation, respectively. This epigenetic modification leads to the downregulation of chemokine genes Cxcl9 and Cxcl10, impeding the recruitment of CD8⁺ T cells. Reduced Cxcl9 secretion by antigen-presenting cells (APCs) following interferon (IFN)-γ exposure is associated with Ccl5 methylation in cancer cells, resulting in diminished CD8⁺ T cell infiltration. Leukemia inhibitory factor (LIF) promotes the recruitment of EZH2 to the Cxcl9 promoter in tumor-associated macrophages (TAMs), contributing to epigenetic silencing. The formation of immunological synapses and antigen presentation is essential for mounting effective cytotoxic responses against tumors. Nevertheless, epigenetic mechanisms, notably DNA methylation, can silence this process within tumor cells. Methylation of genes in PD-1⁺CD8⁺ T cells may induce an exhaustion state, leading to resistance to therapies targeting the PD-1 pathway, such as anti-PD-1 antibodies. In this context, black arrows represent promotion, while red bars symbolize inhibition. This figure was created using Figdraw