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:(1→3)-α-d-Glucooligosaccharides Increase the Killing Capacity of NK Cells against Selected Human Colon Cancer Cells.
(1→3)-α-d-Glucooligosaccharides Increase the Killing Capacity of NK Cells against Selected Human Colon Cancer Cells.
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尽管医学取得了进步,结直肠癌多年来在癌症发病率和死亡率排名中一直占据最高位置之一。因此,人们寻求其替代治疗方法。较新的治疗策略之一是基于NK 细胞的免疫疗法,NK细胞是机体对抗癌症的第一道防线。
本研究旨在验证利用从硫色绚孔菌子实体中(1→3)-α-d-葡聚糖经酸水解获得的(1→3)-α-d-葡寡糖(GOSs)来增强具有已证实临床实用性的NK-92细胞对选定人结肠腺癌细胞系LS180和HT-29的抗癌效果的可能性。研究显示,所研究的寡糖显著增强了NK-92细胞清除所检测结肠癌细胞的能力,主要通过增加其细胞毒活性实现。最显著的效果观察于暴露于由500 µg/mL GOS激活的两倍数量NK细胞的LS180和HT-29细胞,其中NK-92的杀伤特性分别增加了20.5%(p < 0.001)和24.8%(p < 0.001)。(1→3)-α-d-葡寡糖对NK-92抗癌特性的有益影响提示其可作为佐剂用于结肠癌免疫治疗;然而,所获得的数据需要进一步研究和确认。
Despite the progress of medicine, colorectal cancer has occupied one of the highest positions in the rankings of cancer morbidity and mortality for many years.
Thus, alternative methods of its treatment are sought. One of the newer therapeutic strategies is immunotherapy based on NK cells (natural killers), which are the body's first line of defense against cancer. The aim of the study was to verify the possibility of using (1→3)-α-d-glucooligosaccharides (GOSs) obtained via acid hydrolysis of (1→3)-α-d-glucan from the fruiting body of Laetiporus sulphureus to improve the anticancer effect of NK-92 cells, with proven clinical utility, against selected human colon adenocarcinoma cell lines LS180 and HT-29.
The study revealed that the investigated oligosaccharides significantly enhanced the ability of NK-92 cells to eliminate the examined colon cancer cells, mostly by an increase in their cytotoxic activity. The most significant effect was observed in LS180 and HT-29 cells exposed to a two-times higher quantity of NK cells activated by 500 µg/mL GOS, wherein NK-92 killing properties increased for 20.
5% ( p < 0. 001) and 24. 8% ( p < 0. 001), respectively. The beneficial impact of (1→3)-α-d-glucooligosaccharides on the anticancer properties of NK-92 suggests their use in colon cancer immunotherapy as adjuvants; however, the obtained data require further investigation and confirmation.
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