Epigenetic Regulation of NK Cell-Mediated Antitumor Immunity

Natural killer (NK) cells are critical innate lymphocytes that can directly kill target cells without prior immunization. NK cell activation is controlled by the balance of multiple germline-encoded activating and inhibitory receptors. NK cells are a heterogeneous and plastic population displaying a broad spectrum of functional states (resting, activating, memory, repressed, and exhausted). In this review, we present an overview of the epigenetic regulation of NK cell-mediated antitumor immunity, including DNA methylation, histone modification, transcription factor changes, and microRNA expression. NK cell-based immunotherapy has been recognized as a promising strategy to treat cancer. Since epigenetic alterations are reversible and druggable, these studies will help identify new ways to enhance NK cell-mediated antitumor cytotoxicity by targeting intrinsic epigenetic regulators alone or in combination with other strategies.

Automated summary

NK cells are a heterogeneous and plastic population that can directly kill target cells without prior immunization, with their activation controlled by the balance of multiple germline-encoded activating and inhibitory receptors. Epigenetic regulation plays an important role in NK cell-mediated antitumor immunity, and NK cell-based immunotherapy is considered a promising strategy for cancer treatment. By targeting intrinsic epigenetic regulators alone or in combination with other strategies, there is potential to enhance NK cell-mediated antitumor cytotoxicity.