RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Natural killer cell epigenetic reprogramming in tumors and potential for cancer immunotherapy.
Natural killer cell epigenetic reprogramming in tumors and potential for cancer immunotherapy.
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自然杀伤(NK)细胞是固有淋巴样细胞群体中的关键成员,在清除癌症中发挥关键作用。NK 细胞的成熟、发育和功能受到表观遗传修饰的严密调控,而这些修饰也可被肿瘤利用以促进癌症进展和免疫逃逸。NK 细胞具有通过多种表观遗传调控因子被激活以对抗肿瘤的潜力。鉴于表观遗传变化是可诱导且可逆的,聚焦于肿瘤细胞所利用的异常表观遗传调控为癌症治疗提供了巨大机遇。本综述全面呈现了 NK 细胞正常表观遗传调控以及癌症驱动的表观遗传修饰。在我们看来,更好地理解能够编辑和修正 NK 细胞活性的表观遗传调控因子,是 NK 细胞为基础的治疗在癌症管理中一条有前景的途径。自然杀伤(NK)细胞是我们免疫系统中对抗癌症的关键细胞类型之一,尤其是在癌症形成的早期阶段。NK 细胞在骨髓中产生,并在血液中发育为成熟细胞。NK 细胞的发育在我们体内受到不同机制的严密调控,包括遗传和表观遗传因素。与遗传决定因素不同,表观遗传因素可通过多种触发因素被诱导和改变;例如,运动后 NK 细胞活性会增强。癌症具有一种智能功能:它们试图对抗免疫系统并使其功能受损。
因此,癌细胞产生不同物质并利用多种机制抑制 NK 细胞活性。换言之,它们利用表观遗传修饰来制造失活的 NK 细胞。幸运的是,由于表观遗传改变是可逆的,因此有可能逆转表观遗传改变并激活NK细胞对抗癌症。有一些研究表明,在实验室中成功使用表观遗传修饰剂激活NK细胞。
此外,一些研究集中于在不同人类癌症中使用NK细胞行为的表观遗传修饰剂。我们对正常NK细胞中表观遗传修饰了解得越多,基于它们创建抗癌治疗的可能性就越大。
Natural killer (NK) cells are critical members of the innate lymphoid cell population and have a pivotal role in cancer eradication. NK cell maturation, development and function are tightly regulated by epigenetic modifications, which can also be recruited for cancer propagation and immune escape. NK cells have the potential to be activated against tumors through several epigenetic regulators. Given that epigenetic changes are inducible and reversible, focusing on aberrant epigenetic regulations recruited by tumor cells provides a tremendous opportunity for cancer treatment. This review presents a comprehensive picture of NK cell normal epigenetic regulation and cancer-driven epigenetic modifications. From our perspective, a better understanding of epigenetic regulators that can edit and revise NK cells' activity is a promising avenue for NK cell-based therapy in cancer management. Natural killer (NK) cells are one of the critical cell types in our immune system, fighting against cancers, especially in the first stages of cancer formation.
NK cells are produced in the bone marrow and develop to mature cells in the blood. NK cell development is tightly regulated in our body by different mechanisms, including genetic and epigenetic factors. Unlike genetic determinants, epigenetic factors are inducible and changeable via multiple triggers; for example, NK cell activity is enhanced after exercise. Cancers have an intelligent function: they try to counteract the immune system and make it functionally impaired.
So cancer cells produce different substances and use diverse mechanisms to suppress NK cell activity. In other words, they use epigenetic modifications to create inactive NK cells. Fortunately, as the epigenetic changes are reversible, it is possible to reverse epigenetic alterations and activate NK cells against cancers. There are some studies indicating the successful use of epigenetic modifiers in activating NK cells in labs.
Furthermore, some studies have focused on the use of epigenetic modifiers of NK cell behavior in different human cancers. The more we know about the epigenetic modifications in normal NK cells, the higher possibility we have to create an anticancer treatment based on them.
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