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基于患者的多层次转录组探索强调了胶质母细胞瘤中相关趋化因子和趋化因子受体轴。

Patient-based multilevel transcriptome exploration highlights relevant chemokines and chemokine receptor axes in glioblastoma.

机构信息

Immuno-Pharmacology and Interactomics, Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Laboratory of Nervous System Diseases and Therapy, GIGA Neuroscience, GIGA Institute, University of Liège, Belgium.

出版信息

Comput Biol Med. 2024 Nov;182:109197. doi: 10.1016/j.compbiomed.2024.109197. Epub 2024 Sep 30.

Abstract

Chemokines and their receptors form a complex interaction network, crucial for precise leukocyte positioning and trafficking. In cancer, they promote malignant cell proliferation and survival but are also critical for immune cell infiltration in the tumor microenvironment. Glioblastoma (GBM) is the most common and lethal brain tumor, characterized by an immunosuppressive TME, with restricted immune cell infiltration. A better understanding of chemokine-receptor interactions is therefore essential for improving tumor immunogenicity. In this study, we assessed the expression of all human chemokines in adult-type diffuse gliomas, with particular focus on GBM, based on patient-derived samples. Publicly available bulk RNA sequencing datasets allowed us to identify the chemokines most abundantly expressed in GBM, with regard to disease severity and across different tumor subregions. To gain insight into the chemokines-receptor network at the single cell resolution, we explored GBmap, a curated resource integrating multiple scRNAseq datasets from different published studies. Our study constitutes the first patient-based handbook highlighting the relevant chemokine-receptor crosstalks, which are of significant interest in the perspective of a therapeutic modulation of the TME in GBM.

摘要

趋化因子及其受体形成了一个复杂的相互作用网络,对于精确的白细胞定位和迁移至关重要。在癌症中,它们促进恶性细胞的增殖和存活,但对于肿瘤微环境中免疫细胞的浸润也至关重要。胶质母细胞瘤(GBM)是最常见和最致命的脑肿瘤,其特点是免疫抑制性的 TME,免疫细胞浸润受限。因此,更好地了解趋化因子-受体相互作用对于提高肿瘤免疫原性至关重要。在这项研究中,我们根据患者来源的样本评估了所有人类趋化因子在成人弥漫性神经胶质瘤中的表达,特别是在 GBM 中。公共可用的批量 RNA 测序数据集使我们能够确定在 GBM 中表达最丰富的趋化因子,无论疾病的严重程度如何,以及在不同的肿瘤亚区域中。为了深入了解单细胞分辨率下的趋化因子-受体网络,我们探索了 GBmap,这是一个整合了来自不同已发表研究的多个 scRNAseq 数据集的精心整理的资源。我们的研究首次基于患者,强调了相关的趋化因子-受体串扰,这对于在 GBM 中治疗性调节 TME 具有重要意义。

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