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:Phytochemical natural killer cells reprogram tumor microenvironment for potent immunotherapy of solid tumors.
Phytochemical natural killer cells reprogram tumor microenvironment for potent immunotherapy of solid tumors.
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NK 细胞(NKs)在癌症治疗中具有巨大前景,但其在实体瘤中的应用仍面临巨大挑战,因为目前的解决方案几乎无法克服所面临的种种困难。在此,我们赋予NKs植物化学特性,以实现对实体瘤的有效免疫治疗。通过一种高效便捷的膜融合策略,用天然类囊体(Tk)膜对NKs进行修饰。Tk工程化能有效激活NKs,因为Tk上的抗氧化酶诱导糖原合成酶激酶-3β抑制,随后增加NKs中激活性受体和细胞毒性效应分子的表达。全身给药后,植物化学NKs(PC-NKs)能够靶向肿瘤组织,随后借助Tk上的过氧化氢酶深刻重编程肿瘤微环境(TME),从而显著增强PC-NKs的直接杀伤作用和免疫激活的TME。因此,实现了强效的治疗效果且异常反应很少,为开发用于实体瘤的高效NKs提供了新思路。
Natural killer cells (NKs) hold great promise in cancer treatment, but their application in solid tumors remains a great challenge because current solutions hardly can overcome various difficulties that faced.
Herein, we endow NKs with the phytochemical feature for effective immunotherapy of solid tumors. NKs are decorated with natural thylakoid (Tk) membranes through an efficient and convenient membrane fusion strategy. Tk engineering effectively activates NKs, because the antioxidase on Tk induce glycogen synthase kinase-3β inhibition, and subsequently increase the expression of activating receptor and cytotoxic effector molecules in NKs.
After systemic administration, the phytochemical NKs (PC-NKs) can target tumor tissues, and then profoundly reprogram tumor microenvironment (TME) with the help of catalase on Tk, resulting in significantly enhanced direct killing of PC-NKs and immune activated TME.
Therefore, potent therapeutic effects with few abnormalities are achieved, providing a novel idea for the development of highly efficient NKs for solid tumors.
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