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.
肿瘤细胞治疗研究
英文原题:Fucoidan from Durvillaea Antarctica elicits anticancer immunity against lung cancer via natural killer cell activation.
Fucoidan from Durvillaea Antarctica elicits anticancer immunity against lung cancer via natural killer cell activation.
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从海藻中提取的多种多糖具有免疫刺激作用,但仍需鉴定不同海藻中的活性物质,以确定最佳免疫刺激剂。此前已证实,从 Durvillaea antarctica 提取的岩藻多糖(FDA)可激活树突状细胞(DC);然而,FDA 对可直接杀伤肿瘤细胞的 NK 细胞活化有何影响尚未研究。
本研究考察 FDA 对 NK 细胞活化的作用及其治疗肺转移癌的效果。向 C57BL/6 小鼠腹腔给予 FDA 后,脾脏 NK 细胞数量增加,且这些细胞的 Ki67 表达升高。
此外,FDA 处理上调 NK 细胞 CD69 表达,并促进干扰素-γ、穿孔素和颗粒酶 B 产生。FDA 活化的 NK 细胞对 TC-1 肺癌细胞表现出强细胞毒性。给予小鼠 FDA 可减轻 TC-1 肺转移生长。FDA 介导的 NK 细胞活化部分由直接作用、部分由 DC 介导。
最后,在清除 NK 细胞的小鼠中,FDA 对肺转移癌的治疗效果显著减弱。因此,这些数据表明,FDA 可通过活化包括 NK 细胞在内的免疫细胞,减缓肺转移生长。
Several polysaccharides extracted from seaweed have immunostimulatory effects.
However, active substances from various diverse seaweeds should be identified to determine optimal immune stimulators. The dendritic cell (DC) activation ability of fucoidan extracted from Durvillaea antarctica (FDA) has been verified previously.
However, the effect of FDA on the activation of natural killer (NK) cells that can directly kill tumor cells has not been studied. In this study, we investigated the effect of FDA in NK cell activation and examined its therapeutic effect on metastatic lung cancer. Intraperitoneal FDA administration to C57BL/6 mice increased the number of NK cells in the spleen and promoted Ki67 expression in these cells.
In addition, FDA treatment upregulated CD69 in NK cells and interferon- , perforin, and granzyme B production.
Furthermore, FDA-activated NK cells exhibited potent cytotoxicity against TC-1 lung cancer cells. FDA administration to mice attenuated metastatic TC-1 lung cancer growth.
Moreover, the FDA-mediated NK cell activation was partially direct and partially DC-mediated.
Finally, the therapeutic effect of FDA on metastatic lung cancer was significantly weakened in NK cell-depleted mice.
Therefore, these data demonstrated that FDA attenuates lung metastasis growth by activating immune cells including NK cells.
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