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:Experimental study on the induction of cytotoxic T lymphocyte killing effects and dendritic-cell-based tumor vaccine prepared by high-intensity focused ultrasound.
Experimental study on the induction of cytotoxic T lymphocyte killing effects and dendritic-cell-based tumor vaccine prepared by high-intensity focused ultrasound.
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HIFU 制备的抗原致敏 DC 能引起 T 细胞和 CTL 的大量增殖,并具有强抗肿瘤效应。使用 HIFU 照射制备的 DC 肿瘤疫苗在体外影响肿瘤发生的主动免疫,且优于使用反复冻融法制备的 DC 肿瘤疫苗。
本研究旨在探索高强度聚焦超声(HIFU)制备抗原致敏树突状细胞(DC)及DC诱导细胞毒性T淋巴细胞(CTL)杀伤效应,并观察其对BALB/c小鼠的抗肿瘤免疫作用。方法与材料:采用GM-CSF和IL-4培养小鼠骨髓来源DC。使用HIFU制备CT-26肿瘤细胞抗原致敏DC疫苗。采用3 H-TdR检测T细胞增殖能力,采用标准4h 51 Cr释放实验检测CTL细胞毒性。将HIFU照射制备的DC肿瘤疫苗给予正常BALB/c小鼠。7天后将CT-26癌细胞皮下注射至小鼠体内。进一步观察肿瘤发生时间、第20天肿瘤重量和体积,并将单纯采用反复冻融法致敏DC攻击组与生理盐水对照组(阴性对照组)进行比较,分析组间差异。
HIFU组、肿瘤细胞冻融组、肿瘤上清组和磷酸盐缓冲液(PBS)组的DC均能在体外诱导T细胞增殖。然而,HIFU组和肿瘤细胞冻融组DC诱导T细胞增殖的能力显著高于肿瘤上清组和PBS组(P < 0.05)。HIFU组和肿瘤细胞冻融组DC在体外诱导的CTL对结肠癌具有显著细胞毒性,与肿瘤上清组和PBS组相比差异显著(P < 0.05)。HIFU组与肿瘤细胞冻融组体外诱导的CTL细胞毒性之间无显著差异(P > 0.05)。此外,HIFU组、反复冻融组和阴性对照组小鼠在肿瘤发生时间、第20天肿瘤重量和体积以及中位生存时间方面均存在显著差异(P < 0.01或P < 0.05)。HIFU组与反复冻融组之间也存在显著差异(P < 0.05)。
DC in the HIFU group, tumor cell freeze-thawing group, tumor supernatant group, and phosphate buffer solution (PBS) group could induce T cell proliferation in vitro. However, the ability to induce T cell proliferation of DC in the HIFU group and tumor cell freeze-thawing group was significantly higher than those in the tumor supernatant and PBS groups (P < 0. 05). CTL induced in vitro by DC in the HIFU group, and the tumor cell freeze-thawing group had significant cytotoxicity to colon cancer, being significantly different from those in the tumor supernatant and PBS groups (P < 0.05). There was no significant difference between the cytotoxicity of CTL induced in vitro in the HIFU group and the tumor cell freeze-thawing group (P > 0.05). Additionally, significant differences in the occurrence time of the tumor, its weight and volume on the 20 th day, and the median survival time of mice among the HIFU group, the repeated-freezing-thawing group, and the negative control group were observed (P < 0.01 or P < 0.05). There was a significant difference between the HIFU and the repeated-freezing-thawing group (P < 0.05).
HIFU prepared antigen-sensitized DC could cause substantial proliferation of T cells and CTL with strong anti-tumor effects. The DC-based tumor vaccine prepared using HIFU irradiation affected active immunization on the tumor occurrence in vitro and was better than the DC-based tumor vaccine prepared using the repeated-freezing-thawing method.
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