一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
SFXN1 介导的肺腺癌免疫细胞浸润和肿瘤发生：一个潜在的治疗靶点
英文原题：SFXN1-mediated immune cell infiltration and tumorigenesis in lung adenocarcinoma: A potential therapeutic target.
查看英文原题
SFXN1-mediated immune cell infiltration and tumorigenesis in lung adenocarcinoma: A potential therapeutic target.
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研究概要
我们的研究结果表明，SFXN1 可能是 LUAD 治疗的一个潜在治疗靶点。
研究思路结论见上方概要
背景
Sideroflexin 1 (SFXN1) 是一种与一碳代谢相关的线粒体丝氨酸转运蛋白，是肺腺癌 (LUAD) 的预后生物标志物。然而，其在 LUAD 进展中的作用仍不清楚。本研究旨在探讨 SFXN1 在 LUAD 中的功能意义，并评估其作为治疗靶点的潜力。
方法
我们利用泛癌TCGA数据集分析了SFXN1在LUAD中的表达及其诊断和预后价值。采用体外实验（CCK-8、细胞周期、EDU、伤口愈合和transwell）评估SFXN1的作用，并辅以体内实验。RNA测序阐明了SFXN1介导的细胞功能及潜在机制。利用来自TCGA和GEO的bulk RNA-seq和scRNA-seq数据研究SFXN1与肿瘤免疫微环境之间的相关性。RT-qPCR、Western blot和IHC实验验证了SFXN1在LUAD中的表达及其对免疫微环境的影响。
结果
SFXN1在LUAD组织中表达上调，并与不良预后相关。RNA-seq和scRNA-seq分析显示，肿瘤细胞中SFXN1表达增加，伴随NK细胞和细胞毒性T细胞浸润减少。敲低SFXN1显著降低细胞增殖和迁移，其分子机制可能涉及ERK磷酸化和CCL20表达的抑制。在体内，靶向SFXN1减少了Tregs浸润并抑制了肿瘤生长。
展开英文摘要原文
BACKGROUND
Sideroflexin 1 (SFXN1), a mitochondrial serine transporter implicated in one-carbon metabolism, is a prognostic biomarker in lung adenocarcinoma (LUAD). However, its role in LUAD progression remains elusive. This study aimed to investigate the functional significance of SFXN1 in LUAD and evaluate its potential as a therapeutic target.
METHODS
We analyzed SFXN1 expression and its diagnostic and prognostic value in LUAD using the Pan-cancer TCGA dataset. In vitro assays (CCK-8, cell cycle, EDU, wound-healing, and transwell) were employed to assess the role of SFXN1, complemented by in vivo experiments. RNA sequencing elucidated SFXN1-mediated cellular functions and potential mechanisms. Bulk RNA-seq and scRNA-seq data from TCGA and GEO were used to investigate the correlation between SFXN1 and the tumor immune microenvironment. RT-qPCR, Western blot, and IHC assays validated SFXN1 expression and its impact on the immune microenvironment in LUAD.
RESULTS
SFXN1 was upregulated in LUAD tissues and associated with poor prognosis. RNA-seq and scRNA-seq analyses revealed increased SFXN1 expression in tumor cells, accompanied by decreased infiltration of NK and cytotoxic T cells. SFXN1 knockdown significantly reduced cell proliferation and migration, and the inhibition of ERK phosphorylation and CCL20 expression may be the molecular mechanism involved. In vivo, targeting SFXN1 decreased Tregs infiltration and inhibited tumor growth.
CONCLUSIONS
Our findings suggest that SFXN1 may be a potential therapeutic target for LUAD treatment.
论文信息
- 作者
- Li Y、Yang W、Liu C、Zhou S、Liu X、Zhang T、Wu L、Li X
- 第一作者单位
- Department of Anaesthesiology and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, China.China
- 通讯作者单位
- Department of Anaesthesiology and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, China; Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faulty of Medicine, Imperial College London, Chelsea and Westminster Hospital, UK. Electronic address: e.chang17@imperial.ac.uk.China
- 期刊
- International immunopharmacology2024 May 10
- 原文标识
- PubMed 38537539 · DOI 10.1016/j.intimp.2024.111918