Fig. 1.

Epigenetic mechanisms leading to loss of immunogenicity. a Tumor cell (black) maintains expression of tumor-associated antigens (TAA) and immune-related processes, such as antigen presentation machinery, interferon (IFN)-γ receptor, and chemokines CXCL9 and CXCL10. This leads to the accumulation of CD8⁺ T-cells (blue) in the tumor microenvironment and subsequent recognition of tumors via the major histocompatibility complex class-I (MHC-I)—TAA—T-cell receptor (TCR) complex. Infiltrating CD8⁺ and CD4⁺ T-cells (not shown) produce IFN-γ, which further promotes antigen presentation and expression of programmed death-ligand 1 (PD-L1) on tumor cells. Persistent antigen stimulation, interaction of programmed cell death protein-1 (PD-1) and PD-L1 and expression of other inhibitory signals lead to exhaustion of CD8⁺ T-cells. b Tumor cell (gray) loses the expression of the above-mentioned genes due to DNA and histone methylation. Lack of T-cell-attracting chemokines and antigen presentation inhibits T-cell infiltration and tumor recognition