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:Enhanced Proliferation and Activation of Natural Killer Cells by Deer Antler Velvet Extract, YC-1101, and Its Synergistic Antitumor Effects in CT26 Syngeneic Mouse Model.
Enhanced Proliferation and Activation of Natural Killer Cells by Deer Antler Velvet Extract, YC-1101, and Its Synergistic Antitumor Effects in CT26 Syngeneic Mouse Model.
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鹿茸(Cervus elaphus L.)是东方传统医学材料,常用于抗衰老、抗氧化和增强免疫。研究团队此前发现,酶解鹿茸提取物YC-1101可通过激活巨噬细胞并增强脾细胞增殖来刺激免疫系统。本研究考察YC-1101对自然杀伤(NK)细胞增殖、活化及细胞毒性的影响,重点关注活化受体上调、细胞因子分泌和抗肿瘤效能。结果显示,YC-1101通过维持线粒体功能,以剂量和时间依赖方式显著增强NK细胞增殖。经YC-1101扩增的NK细胞表面活化受体NKG2D和NKp44表达显著增加。与对照组相比,YC-1101处理组肿瘤坏死因子α、干扰素γ和粒细胞—巨噬细胞集落刺激因子等免疫相关细胞因子水平显著升高。值得注意的是,YC-1101诱导的NK细胞活化增强了其对多种癌细胞系的细胞毒性;联合免疫检查点抑制可协同增强抗肿瘤活性。综上,YC-1101与扩增NK细胞联合,可能成为提高癌症治疗效果的一种有前景方法。
Deer antler velvet ( Cervus elaphus L.) is a traditional material in oriental medicine, extensively utilized for its anti-aging, antioxidant, and immune-boosting properties.
Our prior research revealed that enzyme-derived deer antler velvet extract (YC-1101) stimulated the immune system by activating macrophages and augmenting splenocyte proliferation. In this study, we investigated the effect of YC-1101 on the proliferation, activation, and cytotoxicity of natural killer (NK) cells, emphasizing activation-receptor upregulation, cytokine secretion, and antitumor efficacy.
Our findings demonstrated that YC-1101 treatment markedly enhanced NK cell proliferation in a dose-dependent and time-dependent manner by preserving mitochondrial function. NK cells expanded through YC-1101 treatment exhibited a significant increase in surface expression of activating NK receptors, NKG2D, and NKp44.
Additionally, levels of immune-related cytokines like tumor necrosis factor-alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor were substantially elevated in the YC-1101-treated group compared with control.
Notably, NK cell activation induced by YC-1101 intensified cytotoxicity against various cancer cell lines, and combining YC-1101 with immune checkpoint inhibition synergistically enhanced antitumor activity. Collectively, our results indicate that integration of YC-1101 with expanded NK cells could be a promising approach to augment cancer treatment efficacy.
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