Fig. 1

Mechanisms by which hypomethylating agents may modulate tumor cells (left) and T cells (right) in the anti-tumor immune response. The hypomethylating agent, decitabine, has activity in tumor cells and T cells in increasing immunogenicity [35, 63]. DAC treatment induces ERV expression in tumor cells, activating the MDA-5/MAVS innate immune sensing pathway, resulting in type I interferon expression [35]. Type I interferons stimulate interferon-stimulated gene (ISG) expression. ERV expression induces the production of aberrant ERV-derived peptides, which are predicted to bind to class I MHC molecules recognized by T cell receptors on CTLs. DAC treatment also impacts anti-tumor CTLs by inducing preferential expression of short isoforms of NFATc1, associated with increased CTL effector function, cytotoxicity and increased survival [63]