CD8A and neoplasm: Tumor antigen overstimulation is doubtlessly a crucial inducer for CD8+ T cell exhaustion, and multiple transcription factors or regulators are identified, such as HMG-box transcription factor TOX, T cell factor-1, and death-associated protein like 1 (Dapl1).325–327 However, the details of how they respond to upstream antigen overstimulation and orchestrate downstream methylome remodeling remain largely unknown.