铂类药物通过ros依赖途径上调CXCR4和PD-L1的表达,对胃癌的新型联合治疗具有重要意义。

IF 3.4 2区 医学 Q1 PATHOLOGY
Xiaoyu Kang, Lin Zhang, Shushang Liu, Fei Wang, Haiming Liu, Fenli Zhou, Fei Wu, Haohao Zhang, Daiming Fan, Yongzhan Nie, Zhangqian Chen
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引用次数: 0

摘要

CXC趋化因子受体4 (CXCR4)和程序性细胞死亡配体1 (PD-L1)是参与肿瘤免疫微环境的两个关键分子。然而,铂类药物(如顺铂)对胃癌(GC)中CXCR4或PD-L1表达的影响及其潜在机制尚不清楚。此外,它们在GC中的表达水平之间的相关性尚不明确。采用免疫组化、western blot、RT-qPCR检测CXCR4和PD-L1在GC中的表达模式。我们利用临床样本、患者来源的异种移植物和细胞来源的异种移植物来研究铂类药物对CXCR4和PD-L1表达水平的影响。化疗后切除的胃癌组织显示CXCR4和PD-L1表达水平高于预处理活检(p
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Platinum drugs upregulate CXCR4 and PD-L1 expression via ROS-dependent pathways, with implications for novel combined treatment in gastric cancer

Platinum drugs upregulate CXCR4 and PD-L1 expression via ROS-dependent pathways, with implications for novel combined treatment in gastric cancer

CXC chemokine receptor 4 (CXCR4) and programmed cell death-ligand 1 (PD-L1) are two critical molecules involved in the tumor immune microenvironment. However, the impact of platinum drugs, such as cisplatin, on CXCR4 or PD-L1 expression and the underlying mechanisms in gastric cancer (GC) remain unknown. Moreover, the correlation between their expression levels in GC remains elusive. Immunohistochemistry, western blot, and RT-qPCR were performed to determine the expression pattern of CXCR4 and PD-L1 in GC. Clinical samples, patient-derived xenografts, and cell-derived xenografts were utilized to investigate the effects of platinum drugs on the expression levels of CXCR4 and PD-L1. Postchemotherapy resected GC tumor tissues showed higher CXCR4 and PD-L1 expression levels than pretreatment biopsies (p < 0.05). Similarly, GC xenografts treated with platinum-based chemotherapy exhibited increased CXCR4 and PD-L1 expression levels compared to saline-treated controls (p < 0.05). A positive correlation was detected between the expression levels of CXCR4 and PD-L1 in GC tumor tissues. Increased levels of CXCR4 and PD-L1 expression, in a dose- and time-dependent manner upon cisplatin treatment, were observed in GC cells (p < 0.05). Cisplatin-induced CXCR4 upregulation relies on ROS/HIF-1α and ROS/NF-κB pathways, while cisplatin-induced PD-L1 upregulation is cyclic GMP-AMP synthase/stimulator of IFN genes-dependent and associated with elevated ROS levels in GC cells. CXCR4 expression was found to be positively correlated with PD-L1 expression in GC. Platinum drugs upregulated the levels of CXCR4 and PD-L1 expression in GC. A combined strategy targeting CXCR-4 and PD-L1 might have clinical prospects for GC patients.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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