Abstract
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.
Highlights
Natural killer (NK) cells are potent effector lymphocytes of the innate immune system
In addition to direct cytotoxic activity, NK cells can function as central communicators of innate and adaptive immunity in the tumor microenvironment (TME) by secreting multiple chemokines (CCL3, CCL4, CCL5, and XCL1), cytokines (IFN-g, Transforming growth factor-b (TGF-b), and IL10), and growth factors (GM-CSF) [7]
We provide an overview of the epigenetic regulators that modulate NK cell-based antitumor immunity, and the findings will hopefully help to identify novel approaches and potential targets for tumor immunotherapy
Summary
Natural killer (NK) cells are potent effector lymphocytes of the innate immune system. In addition to direct cytotoxic activity, NK cells can function as central communicators of innate and adaptive immunity in the TME by secreting multiple chemokines (CCL3, CCL4, CCL5, and XCL1), cytokines (IFN-g, TGF-b, and IL10), and growth factors (GM-CSF) [7]. In this way, these cells communicate with various immune cells within tumor tissues, including monocytes, granulocytes, dendritic cells, T cells, and stromal cells [8]. The “ready-to-go” state is associated with the unique epigenetic features of NK cells, as shown
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