Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany.
Front Immunol. 2022 May 30;13:913054. doi: 10.3389/fimmu.2022.913054. eCollection 2022.
Natural Killer cells (NK cells) are cytotoxic innate lymphoid cells (ILCs), which play a key role in the early protection against viral infection and cancer. In addition to mounting rapid effector responses, NK cells possess the capacity to generate long-lived memory cells in response to certain stimuli, thus blurring the lines between innate and adaptive immunity and making NK cells an ideal candidate for tumor immunotherapy. NK cell development, activation and memory formation are regulated by epigenetic alterations driven by a complex interplay of external and internal signals. These epigenetic modifications can convey long-lasting functional and phenotypic changes and critically modify their response to stimulation. Here, we review how NK cell functionality and plasticity are regulated at the epigenetic level in different tissue microenvironments and within tumor microenvironments. An in-depth understanding of the epigenetic modifications underlying NK cell functional diversity in different environments is an essential step in the development of NK cell-based cancer therapies.
自然杀伤细胞（NK 细胞）是细胞毒性先天淋巴细胞（ILC），在早期对抗病毒感染和癌症方面发挥着关键作用。除了迅速产生效应反应外，NK 细胞还具有针对某些刺激产生长寿命记忆细胞的能力，从而模糊了先天免疫和适应性免疫之间的界限，使 NK 细胞成为肿瘤免疫治疗的理想候选者。NK 细胞的发育、激活和记忆形成受表观遗传改变的调控，这些改变是由外部和内部信号的复杂相互作用驱动的。这些表观遗传修饰可以传递持久的功能和表型变化，并对它们对刺激的反应产生重大影响。在这里，我们综述了 NK 细胞在不同组织微环境中和肿瘤微环境中，在表观遗传水平上如何调控其功能和可塑性。深入了解 NK 细胞在不同环境中功能多样性的表观遗传修饰，是开发基于 NK 细胞的癌症治疗方法的重要步骤。
