PDF(Pubmed)
Abstract：
Non-small cell lung cancer (NSCLC) represents a highly immunogenic malignancy. Immunologic tolerance facilitated by myeloid-derived suppressor cells (MDSCs) is implicated in primary or secondary resistance mechanisms in NSCLC. The potential role of APE1 in regulating NSCLC metastasis by targeting MDSCs remains uncertain.
This study utilized a plasmid, Plxpsp-mGM-CSF, to induce elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in A549 cells. Tumor transplantation experiments involved A549, A549+GM-CSF, and A549+GM-CSF-siAPE1 cell lines. Evaluation encompassed MDSCs, Treg cells, IgG, CD3, and CD8 levels.
Notably, lung cancer tissues and cells displayed markedly reduced APE1 expression. siAPE1 transfection significantly curtailed tumor growth compared to the A549+GM-CSF group. APE1 knockdown orchestrated immune system modulation in lung tumor mice, characterized by diminished MDSCs but augmented Treg cells, IgG, CD3, and CD8. Additionally, APE1 knockdown led to reduced levels of pro-MDSC cytokines (HGF, CCL5, IL-6, CCL12) and a concurrent upregulation of the anti-MDSC cytokine IL-1ra. Furthermore, APE1 knockdown impeded cell viability in both A549 and H1650 cells.
Transplantation of A549-GM-CSF amplified MDSC levels, fostering accelerated tumor growth, while mitigating MDSC levels through APE1 knockdown hindered tumor progression and alleviated inflammatory infiltration in lung cancer tissues. Strategies targeting the APE1/MDSC axis offer a promising approach for lung cancer prevention and treatment, presenting novel insights for NSCLC management.
This study utilized a plasmid, Plxpsp-mGM-CSF, to induce elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in A549 cells. Tumor transplantation experiments involved A549, A549+GM-CSF, and A549+GM-CSF-siAPE1 cell lines. Evaluation encompassed MDSCs, Treg cells, IgG, CD3, and CD8 levels.
Notably, lung cancer tissues and cells displayed markedly reduced APE1 expression. siAPE1 transfection significantly curtailed tumor growth compared to the A549+GM-CSF group. APE1 knockdown orchestrated immune system modulation in lung tumor mice, characterized by diminished MDSCs but augmented Treg cells, IgG, CD3, and CD8. Additionally, APE1 knockdown led to reduced levels of pro-MDSC cytokines (HGF, CCL5, IL-6, CCL12) and a concurrent upregulation of the anti-MDSC cytokine IL-1ra. Furthermore, APE1 knockdown impeded cell viability in both A549 and H1650 cells.
Transplantation of A549-GM-CSF amplified MDSC levels, fostering accelerated tumor growth, while mitigating MDSC levels through APE1 knockdown hindered tumor progression and alleviated inflammatory infiltration in lung cancer tissues. Strategies targeting the APE1/MDSC axis offer a promising approach for lung cancer prevention and treatment, presenting novel insights for NSCLC management.
摘要：
背景：非小细胞肺癌（NSCLC）是一种高度免疫原性的恶性肿瘤。骨髓来源的抑制细胞（MDSC）促进的免疫耐受与NSCLC的原发性或继发性耐药机制有关。APE1通过靶向MDSCs在调节NSCLC转移中的潜在作用仍不确定。
方法：本研究利用质粒，Plxpsp-mGM-CSF,在A549细胞中诱导粒细胞-巨噬细胞集落刺激因子(GM-CSF)表达升高。肿瘤移植实验涉及A549，A549+GM-CSF，和A549+GM-CSF-siAPE1细胞系。评估包括MDSCs，Treg细胞,IgG,CD3和CD8水平。
结果：值得注意的是，肺癌组织和细胞显示APE1表达明显降低。与A549+GM-CSF组相比,siAPE1转染显著减少了肿瘤生长。APE1敲低了肺癌小鼠的免疫系统调节，以MDSCs减少但Treg细胞增加为特征，IgG,CD3和CD8。此外,APE1敲低导致pro-MDSC细胞因子水平降低(HGF，CCL5，IL-6，CCL12）和抗MDSC细胞因子IL-1ra的同时上调。此外，APE1敲低阻碍了A549和H1650细胞中的细胞活力。
结论：A549-GM-CSF移植扩增了MDSC水平，促进肿瘤加速生长，而通过APE1敲低减轻MDSC水平阻碍了肿瘤进展并减轻了肺癌组织中的炎症浸润。针对APE1/MDSC轴的策略为肺癌的预防和治疗提供了一种有希望的方法，为非小细胞肺癌管理提供新的见解。
方法：本研究利用质粒，Plxpsp-mGM-CSF,在A549细胞中诱导粒细胞-巨噬细胞集落刺激因子(GM-CSF)表达升高。肿瘤移植实验涉及A549，A549+GM-CSF，和A549+GM-CSF-siAPE1细胞系。评估包括MDSCs，Treg细胞,IgG,CD3和CD8水平。
结果：值得注意的是，肺癌组织和细胞显示APE1表达明显降低。与A549+GM-CSF组相比,siAPE1转染显著减少了肿瘤生长。APE1敲低了肺癌小鼠的免疫系统调节，以MDSCs减少但Treg细胞增加为特征，IgG,CD3和CD8。此外,APE1敲低导致pro-MDSC细胞因子水平降低(HGF，CCL5，IL-6，CCL12）和抗MDSC细胞因子IL-1ra的同时上调。此外，APE1敲低阻碍了A549和H1650细胞中的细胞活力。
结论：A549-GM-CSF移植扩增了MDSC水平，促进肿瘤加速生长，而通过APE1敲低减轻MDSC水平阻碍了肿瘤进展并减轻了肺癌组织中的炎症浸润。针对APE1/MDSC轴的策略为肺癌的预防和治疗提供了一种有希望的方法，为非小细胞肺癌管理提供新的见解。
