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:Natural adjuvants (PC and G2) induce activated natural killer cells with NKG2D expression and cytotoxic properties in colorectal cancer.
Natural adjuvants (PC and G2) induce activated natural killer cells with NKG2D expression and cytotoxic properties in colorectal cancer.
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根据本研究的结果,可以认为 PC 和 G2 佐剂可能是诱导细胞毒性 NK 细胞的候选物。
自然杀伤(NK)细胞是先天免疫系统的一个组成部分,能够识别并杀伤癌细胞,为癌症治疗带来了希望。目前癌症免疫治疗方法之一是NK细胞疗法。由于NK细胞数量和细胞毒性水平较低,NK细胞免疫治疗受到限制。PC和G2等天然佐剂可能刺激免疫系统。这些佐剂似乎可以增加细胞毒性NK细胞。
本研究旨在探讨天然佐剂(G2和PC)在结直肠癌中激活NK 细胞的效果。
12例结直肠癌患者和6名健康个体符合纳入本研究的条件。将每例患者的外周血单个核细胞(PBMCs)以两种不同浓度(10 5和5 10 4个细胞/孔)分别用Interleukin2(IL2)、PC和G2佐剂处理。通过流式细胞术评估NK细胞表面标志物,包括CD16、CD56和NKG2D。采用LDH检测法评估处理后的PBMCs作为效应细胞对NK敏感细胞系(K562)的细胞毒性作用。
结果显示,与对照组相比,G2组处理的PBMC中CD16+NKG2D+ NK细胞水平在CRC PBMC中显著升高(p <0.001),在正常PBMC组中也显著升高(p <0.01)。此外,结果表明,与PBMC组相比,PC组(p <0.05)和G2组(p <0.001)处理的PBMC中CD56+NKG2D+细胞水平显著升高。CRC患者PBMC在效靶比10:1时的细胞毒性结果显示,PC组(p <0.01)和G2组(p <0.05)处理的PBMC细胞毒性显著高于未处理的PBMC。
Natural killer (NK) cells are an element of the innate immune system that can recognize and kill cancer cells and provide hope for cancer therapy. One of the current methods in cancer immunotherapy is NK cell therapy. Immunotherapy with NK cells has been limited because of the low number and cytotoxicity level of NK cells. Natural adjuvants such as PC and G2 may stimulate the immune system. It seems that these adjuvants could increase cytotoxic NK cells.
Twelve patients with colorectal cancer and six healthy individuals qualified for inclusion in this study. Peripheral blood mononuclear cells (PBMCs) from each patient with two distinctive concentrations (10 5 and 5 10 4 cells/well) were treated with Interleukin2 (IL2), PC , and G2 adjuvant separately. The NK cell's surface markers, including CD16, CD56, and NKG2D, were evaluated by flow cytometry. The cytotoxicity effect of treated PBMCs as effector cells against NK sensitive cell line (K562) was assessed using the LDH assay method.
The results revealed a significant increase in the level of CD16+NKG2D+ NK cells in PBMCs treated with the G2 group compared with the control group in CRC PBMC ( p <0.001) as well as the normal PBMC group ( p < 0.01). In addition, the results indicated a significant increase in the level of CD56+NKG2D+ cells in the PBMC treated with PC ( p < 0.05) and G2 ( p < 0.001) groups compared with the PBMC group. The cytotoxicity result of PBMC from CRC patients in 10:1 ratio of the effector: target showed that the cells ' cytotoxicity in the PBMCs treated with PC ( p <0.01) and G2 ( p <0.05) was significantly higher than the untreated PBMC.
According to the result of this study, it can be stated that the PC and G2 adjuvants could be candidates for inducing cytotoxic natural killer cells.
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