PO.MCB09.01 · 分子与细胞生物学
使用成像质谱流式技术对乳腺癌肿瘤微环境中代谢和细胞信号异质性进行空间蛋白质组学分析
Spatial proteomic profiling of metabolic and cell signaling heterogeneity in breast cancer tumor microenvironment using imaging mass cytometry
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摘要 Abstract
中文摘要
肿瘤微环境（TME）是由肿瘤细胞和免疫细胞组成的复杂生态系统，其代谢和信号通路失调，驱动肿瘤异质性、进展和差异化治疗反应。靶向这些通路已成为增强免疫治疗疗效的一种有希望的策略。成像质谱流式技术™（IMC™）系统利用CyTOF™技术，能够同时检测>40种标志物，提供可扩展、高通量的TME空间表征，具有真正的动态范围，不受基于荧光方法固有的光谱重叠和自发荧光限制的影响。
我们应用IMC技术，使用整合抗体panel解析人类乳腺癌中的代谢和信号程序：将Human Immuno-Oncology IMC Panel（PN 201509）与Human Cell Metabolism（PN 201521）或Human Cell Signaling（PN 201522）IMC Panels相结合。这种方法能够同时评估能量产生、细胞稳态和促有丝分裂信号。全组织切片最初在Preview模式下成像，随后使用Cell模式或Tissue模式对感兴趣区域进行高分辨率分析，以对肿瘤和免疫细胞进行表型分析并评估免疫激活。
IMC技术揭示了乳腺肿瘤内代谢和信号状态的空间异质性。肿瘤区域表现出差异化的能量利用：免疫细胞主要浸润富含脂肪酸氧化的区域，而具有无氧或有氧糖酵解的肿瘤区域对应于免疫排斥区。信号通路活性也因细胞类型而异。糖酵解升高和mTOR激活表明对缺氧和合成代谢需求的适应。Wnt信号和PTEN表达在肿瘤细胞中富集，而MAP激酶信号主要定位于基质区室。使用MCD™ SmartViewer进行的无监督像素聚类和层次分析进一步解析了区域特异性的代谢和信号异质性。
IMC系统能够对乳腺癌中的代谢和信号进行全面的空间分析，揭示肿瘤-免疫相互作用和瘤内异质性。这种高维空间分辨方法为鉴定临床相关靶点、指导预后评估和引导个体化治疗策略的开发提供了强大的框架。
仅供研究使用。不用于诊断程序。
查看英文原文 English abstract
The tumor microenvironment (TME) is a complex ecosystem of tumor and immune cells with dysregulated metabolic and signaling pathways that drive tumor heterogeneity, progression and differential treatment response. Targeting these pathways has emerged as a promising strategy to enhance immunotherapy efficacy. Imaging Mass Cytometry™ (IMC™) systems, leveraging CyTOF™ technology, enable simultaneous detection of >40 markers, providing scalable, high-throughput spatial characterization of the TME with true dynamic range, free from spectral overlap and autofluorescence limitations inherent to fluorescence-based approaches.
We applied IMC technology to interrogate metabolic and signaling programs in human breast cancer using integrated antibody panels: the Human Immuno-Oncology IMC Panel (PN 201509) combined with either the Human Cell Metabolism (PN 201521) or Human Cell Signaling (PN 201522) IMC Panels. This approach enabled simultaneous assessment of energy production, cellular homeostasis and mitogenic signaling. Whole tissue sections were initially imaged in Preview Mode, followed by high-resolution analysis of regions of interest using Cell Mode or Tissue Mode to phenotype tumor and immune cells and evaluate immune activation.
IMC technology revealed spatial heterogeneity in metabolic and signaling states within breast tumors. Tumor regions demonstrated differential energy utilization: Immune cells predominantly infiltrated areas enriched for fatty acid oxidation, whereas tumor regions with anaerobic or aerobic glycolysis corresponded to immune-excluded zones. Signaling pathway activity also varied by cell type. Elevated glycolysis and mTOR activation indicated adaptation to hypoxic and anabolic demands. Wnt signaling and PTEN expression were enriched in tumor cells, whereas MAP kinase signaling was localized primarily to stromal compartments. Unsupervised pixel-clustering and hierarchical analysis using MCD™ SmartViewer further resolved region-specific metabolic and signaling heterogeneity.
IMC systems enable comprehensive spatial profiling of metabolism and signaling in breast cancer, revealing tumor-immune interactions and intratumoral heterogeneity. This high-dimensional spatially resolved approach provides a powerful framework for identifying clinically relevant targets, informing prognostic assessments and guiding development of personalized therapeutic strategies.
For Research Use Only. Not for use in diagnostic procedures.
利益披露 Disclosure
Q. Raza, None..
N. Zabinyakov, None.