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:Korean Red Ginseng Enhances Immunotherapeutic Effects of NK Cells via Eosinophils in Metastatic Liver Cancer Model.
Korean Red Ginseng Enhances Immunotherapeutic Effects of NK Cells via Eosinophils in Metastatic Liver Cancer Model.
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肝癌转移会降低患者生存率,因此亟需新的抗转移策略。韩国红参(KRG)常作为具有增强免疫作用的功能性食品摄入。本研究考察联合使用KRG和自然杀伤(NK)细胞作为新型免疫疗法的可能性。研究将SK-Hep1细胞经尾静脉注入NRGA小鼠,建立实验性转移模型,并分别给予KRG、NK细胞或二者联合治疗。通过活体成像观察肿瘤生长,并以组织学和免疫组化评估转移病灶。KRG与NK细胞联合组的生物发光强度低于其他组,提示联合治疗抑制了转移进展。研究以CD56作为NK细胞标志物,并进行血液学分析。联合治疗还降低了基质金属蛋白酶表达以及肝脏和骨组织内的转移灶面积,同时提高嗜酸性粒细胞计数。通过Western blot检测嗜酸性粒细胞和NK细胞相关细胞因子的表达。KRG与NK细胞联合治疗诱导白细胞介素33(IL-33)表达;Kaplan-Meier Plotter分析显示,IL-33高表达与总生存期延长相关。结果提示,KRG可能通过嗜酸性粒细胞介导的IL-33途径增强NK细胞免疫活性,从而抑制转移性肝癌进展。
Metastasis decreases the survival rate of patients with liver cancer.
Therefore, novel anti-metastatic strategies are needed. Korean Red Ginseng (KRG) is often ingested as a functional food with an immune-boosting effect.
We investigated a combination of KRG and natural killer (NK) cells as a novel immunotherapy approach. SK-Hep1 cells were injected into the tail vein of NRGA mice to establish an experimental metastasis model. KRG, NK cells, or a combination of KRG and NK cells were administered. Tumor growth was observed using an in vivo imaging system, and metastatic lesions were evaluated by histological analysis and immunohistochemistry. Bioluminescence intensity was lower in the KRG and NK cell combination group than in the other groups, indicating that the combination treatment suppressed the progression of metastasis.
CD56 expression was used as a NK cell marker and hematological analysis was performed. The combination treatment also decreased the expression of matrix metalloproteinases and the area of metastatic lesions in liver and bone tissues, as well as increased the eosinophil count.
Expression of cytokines-related eosinophils and NK cells was determined by Western blotting analysis. The expression of interleukin 33 (IL33) was induced by the combination of KRG and NK cells. High IL33 expression was associated with prolonged overall survival in the Kaplan-Meier plotter.
Our results suggest that KRG enhances the immune activity of NK cells by IL-33 through eosinophils and suppresses metastatic liver cancer progression.
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