Interferon signaling and ferroptosis in tumor immunology and therapy

IF 6.8 1区 医学 Q1 ONCOLOGY NPJ Precision Oncology Pub Date : 2024-08-10 DOI:10.1038/s41698-024-00668-w
Wei Hu, Ziqian Zhao, Jianxin Du, Jie Jiang, Minghao Yang, Maojin Tian, Peiqing Zhao
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Abstract

This study sought to elucidate the mechanisms underlying the impact of the interferon signaling pathway on Ferroptosis in tumor cells and its correlation with CD8 + T cell exhaustion. Using mouse models and single-cell sequencing, the researchers studied the interaction between CD8 + T cells and the interferon signaling pathway. Differential gene analysis revealed key genes involved in CD8 + T cell exhaustion, and their downstream factors were explored using bioinformatics tools. The expression levels of interferon-related genes associated with Ferroptosis were analyzed using data from the TCGA database, and their relevance to tumor tissue Ferroptosis and patients’ prognosis was determined. In vitro experiments were conducted to measure the levels of IFN-γ, MDA, and LPO, as well as tumor cell viability and apoptosis. In vivo validation using a mouse tumor model confirmed the results obtained from the in vitro experiments, highlighting the potential of silencing HSPA6 or DNAJB1 in enhancing the efficacy of PD-1 therapy and inhibiting tumor growth and migration.

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肿瘤免疫学和治疗中的干扰素信号传导和铁蛋白沉积。
这项研究试图阐明干扰素信号通路对肿瘤细胞铁凋亡的影响机制及其与CD8 + T细胞衰竭的相关性。研究人员利用小鼠模型和单细胞测序技术,研究了CD8 + T细胞与干扰素信号通路之间的相互作用。差异基因分析揭示了参与CD8 + T细胞衰竭的关键基因,并利用生物信息学工具探索了这些基因的下游因子。利用TCGA数据库的数据分析了与铁锈色素沉着相关的干扰素相关基因的表达水平,并确定了它们与肿瘤组织铁锈色素沉着和患者预后的相关性。体外实验测量了 IFN-γ、MDA 和 LPO 的水平,以及肿瘤细胞的活力和凋亡。利用小鼠肿瘤模型进行的体内验证证实了体外实验所获得的结果,突显了沉默 HSPA6 或 DNAJB1 在提高 PD-1 疗效、抑制肿瘤生长和迁移方面的潜力。
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来源期刊
CiteScore
9.90
自引率
1.30%
发文量
87
审稿时长
18 weeks
期刊介绍: Online-only and open access, npj Precision Oncology is an international, peer-reviewed journal dedicated to showcasing cutting-edge scientific research in all facets of precision oncology, spanning from fundamental science to translational applications and clinical medicine.
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