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单细胞RNA测序和蛋白质组学揭示心脏黏液瘤中SIRPα-CD47免疫检查点及糖酵解驱动的免疫逃逸

Single-cell RNA sequencing and proteomics uncover SIRPα-CD47 immune checkpoint and glycolysis-driven immune evasion in cardiac myxoma.

作者信息

Zhu Xinyuan, Gao Qingle, Dai Xintong, Sun Baofa, Li Yanping, Zhai Hongyan, Shan Changliang

机构信息

Department of Cardiovascular Surgery, The Fifth Central Hospital of Tianjin, Tianjin, China.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.

出版信息

Front Immunol. 2025 Sep 1;16:1652645. doi: 10.3389/fimmu.2025.1652645. eCollection 2025.

DOI:10.3389/fimmu.2025.1652645
PMID:40959090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12433983/
Abstract

Cardiac myxoma (CM), a rare primary cardiac tumor, poses significant life-threatening risks. Current CM research has remained largely limited to clinical case observations and pathological analyses, thus restricting its clinical therapeutic impact. Fundamental research should be urgently strengthened to better support future CM treatment strategies. In this work, single-cell sequencing is used to elucidated the intricate cellular composition of the CM microenvironments. The mechanisms of heart myxoma cell growth are investigated via proteomics and organoid models, while our western blot analysis reveals cardiac myxoma's immune evasion strategies. This study successfully characterizes diverse cell types within the CM microenvironment. Notably, ap-CAF cells are found to effectively recruit immune cells via chemokine secretion, fostering immune microenvironment formation. The work's pseudotime trajectory analysis also demonstrates that CM tumor cells derive from mesenchymal stem cells. Additionally, this work demonstrated that the glycolysis pathway is significantly activated and fuels CM cell growth. Tumor cells exploit the SIRPα-CD47 immune checkpoint to evade the immune system by inhibiting antigen-presenting cell phagocytosis. Tumor-associated macrophages (TAMs) concurrently assume M2 polarization and suppress autoimmune activity through . This research comprehensively examines CM's microenvironmental cellular architecture, metabolic features, and immune escape mechanisms. These work's findings not only deepen the current understanding of CM's biological nature but also offer vital theoretical foundations for developing safer, more effective CM therapies.

摘要

心脏黏液瘤(CM)是一种罕见的原发性心脏肿瘤,具有重大的危及生命的风险。目前对CM的研究在很大程度上仍局限于临床病例观察和病理分析,从而限制了其临床治疗效果。应紧急加强基础研究,以更好地支持未来的CM治疗策略。在这项工作中,单细胞测序被用于阐明CM微环境复杂的细胞组成。通过蛋白质组学和类器官模型研究心脏黏液瘤细胞生长的机制,而我们的蛋白质印迹分析揭示了心脏黏液瘤的免疫逃逸策略。这项研究成功地表征了CM微环境中的多种细胞类型。值得注意的是,发现ap-CAF细胞通过分泌趋化因子有效地招募免疫细胞,促进免疫微环境的形成。该工作的伪时间轨迹分析还表明,CM肿瘤细胞来源于间充质干细胞。此外,这项工作表明糖酵解途径被显著激活并为CM细胞生长提供能量。肿瘤细胞利用SIRPα-CD47免疫检查点通过抑制抗原呈递细胞的吞噬作用来逃避免疫系统。肿瘤相关巨噬细胞(TAM)同时呈现M2极化并通过……抑制自身免疫活性。这项研究全面考察了CM的微环境细胞结构、代谢特征和免疫逃逸机制。这些工作的发现不仅加深了目前对CM生物学性质的理解,也为开发更安全、更有效的CM治疗方法提供了重要的理论基础。

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本文引用的文献

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Resolving the heterogeneous tumour microenvironment in cardiac myxoma through single-cell and spatial transcriptomics.
通过单细胞和空间转录组学解析心脏黏液瘤中的异质性肿瘤微环境
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IL-4 and IL-13 induce equivalent expression of traditional M2 markers and modulation of reactive oxygen species in human macrophages.IL-4 和 IL-13 诱导人巨噬细胞中传统 M2 标志物的同等表达和活性氧的调节。
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Co-stimulatory and immune checkpoint molecules are important in the tumor microenvironment of Hodgkin-like adult T-cell leukemia/lymphoma.共刺激分子和免疫检查点分子在霍奇金样成人T细胞白血病/淋巴瘤的肿瘤微环境中起重要作用。
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