PRPS2-mediated modulation of the antitumor immune response in lung cancer through CCL2-mediated tumor-associated macrophages and myeloid-derived suppressor cells.

IF 2.3 3区 医学 Q3 ONCOLOGY
Thoracic Cancer Pub Date : 2024-08-01 Epub Date: 2024-07-01 DOI:10.1111/1759-7714.15398
Qing Liu, Ningzi Wu, Peifeng Hou
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引用次数: 0

Abstract

Background: Phosphoribosyl pyrophosphate synthetase 2 (PRPS2) is known as an oncogene in many types of cancers, including lung cancer. However, its role in regulating tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) remains unclear. Our study aimed to explore the involvement of PRPS2 in TAM and MDSC regulation.

Methods: Stable Lewis lung cancer (LLC) cell lines were established using a lentivirus system. These LLC lines were then used to establish tumor model in mice. The levels of target genes were determined using qPCR, western blotting, and ELISA assays. The percentage of different immune cell types was analyzed using fluorescence-activated cell sorting. The chemotaxis ability of TAM and MDSC was evaluated using an in vitro transwell chemotaxis assay.

Results: Notably, PRPS2 was found to regulate the chemotaxis of TAM and MDSC in tumor cells, as evidenced by the positive correlation of PRPS2 expression levels and abundance of TAM and MDSC populations. In addition, the expression of CCL2, mediated by PRPS2, was identified as a key factor in the chemotaxis of TAM and MDSC, as evidenced by a significant reduction in macrophages and MDSC numbers in the presence of the CCL2 antibody. Furthermore, in vivo experiments confirmed the involvement of PRPS2 in mediating CCL2 expression. PRPS2 was also found to regulate immune cell infiltration into tumors, whereas knockdown of CCL2 reversed the phenotype induced by PRPS2 overexpression. In tumor tissues from mice implanted with LLC-PRPS2-shCCL2 cells, a notable increase in CD4+ and CD8+ T cell percentages, alongside a marked decrease in TAMs, M-MDSC, and PMN-MDSC, was observed.

Conclusion: Taken together, PRPS2 plays a crucial role in modulating the antitumor immune response by reprogramming CCL2-mediated TAM and MDSC.

PRPS2通过CCL2介导的肿瘤相关巨噬细胞和髓源性抑制细胞调节肺癌的抗肿瘤免疫反应
背景:众所周知,磷酸核糖焦磷酸合成酶 2(PRPS2)是包括肺癌在内的多种癌症的致癌基因。然而,它在调节肿瘤相关巨噬细胞(TAM)和髓源性抑制细胞(MDSC)中的作用仍不清楚。我们的研究旨在探索PRPS2参与TAM和MDSC调控的情况:方法:利用慢病毒系统建立了稳定的路易斯肺癌(LLC)细胞系。方法:使用慢病毒系统建立稳定的 Lewis 肺癌(LLC)细胞系,然后用这些 LLC 系建立小鼠肿瘤模型。使用 qPCR、Western 印迹和 ELISA 检测法确定靶基因的水平。利用荧光激活细胞分拣技术分析了不同免疫细胞类型的百分比。使用体外跨孔趋化试验评估了 TAM 和 MDSC 的趋化能力:结果:值得注意的是,PRPS2能调控肿瘤细胞中TAM和MDSC的趋化,PRPS2的表达水平与TAM和MDSC群体的丰度呈正相关。此外,由 PRPS2 介导的 CCL2 的表达被确定为 TAM 和 MDSC 趋化的一个关键因素,在 CCL2 抗体存在的情况下,巨噬细胞和 MDSC 的数量显著减少就是证明。此外,体内实验证实了 PRPS2 参与介导 CCL2 的表达。研究还发现,PRPS2 可调节免疫细胞对肿瘤的浸润,而 CCL2 的敲除可逆转 PRPS2 过表达所诱导的表型。在植入LLC-PRPS2-shCCL2细胞的小鼠肿瘤组织中,观察到CD4+和CD8+T细胞百分比显著增加,同时TAMs、M-MDSC和PMN-MDSC明显减少:综上所述,PRPS2通过重编程CCL2介导的TAM和MDSC,在调节抗肿瘤免疫反应中发挥着至关重要的作用。
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来源期刊
Thoracic Cancer
Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM
CiteScore
5.20
自引率
3.40%
发文量
439
审稿时长
2 months
期刊介绍: Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.
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