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CyTOF 和成像质谱流式揭示的肿瘤-免疫微环境模式的泛癌趋同

英文原题:Pan-cancer convergence of tumour-immune microenvironment motifs revealed by CyTOF and imaging mass cytometry.

PubMed 2025/10/06(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

46项研究仅使用CyTOF,12项仅采用IMC,3项结合了两种平台。

中文摘要

质谱流式细胞术(CyTOF)和成像质谱流式细胞术(IMC)可对50多种蛋白质标志物实现单细胞分辨率检测,为探索肿瘤和免疫异质性提供了前所未有的手段。我们对61项原始研究(建库至2025年)进行了范围综述,涵盖17种癌症类型,以梳理当前应用、分析策略及新兴的生物学见解。46项研究仅使用CyTOF,12项仅使用IMC,3项联合使用两种平台。CyTOF panel中位标志物数为33.5个,IMC为33个。谱系标志物和免疫检查点标志物普遍使用,而磷酸化表位、代谢酶和基质蛋白则出现在更为聚焦的亚组中。大多数研究遵循三步分析流程:(i)分割或设门,(ii)无监督聚类,(iii)下游空间或功能分析。CyTOF研究常鉴定出耗竭CD8+ T细胞亚群(如PD-1+ TIM-3+ CD39+)、抑制性髓系细胞群(如CD163+ HLA-DR- 巨噬细胞)以及代谢重编程的Tregs。IMC研究揭示了可预测预后的空间模式,如三级淋巴结构(TLSs)和巨噬细胞-T细胞排斥区。若干研究提出了预测性免疫特征或将CyTOF与转录组或空间数据集整合。我们识别出五个反复出现的免疫生物学基序:CD8+ T细胞分叉、CD38+ TAM屏障、TLS成熟度、CTLA-4+ NK细胞特征以及代谢定义的生态位,突出了耐药与应答的汇聚轴线。生物信息学流程趋同于FlowSOM或PhenoGraph聚类、CITRUS或弹性网特征选择,以及日益增多的机器学习和基于智能体的空间建模。总体而言,CyTOF和IMC正在重新定义肿瘤学中的生物标志物发现、治疗分层和虚拟试验设计,确立高维CyTOF作为下一代精准癌症医学的基石。

展开英文摘要原文

Mass cytometry (CyTOF) and Imaging Mass Cytometry (IMC) provide single-cell resolution for over 50 protein markers, enabling unprecedented exploration of tumour and immune heterogeneity. We conducted a scoping review of 61 original studies (inception-2025), spanning 17 cancer types, to map current applications, analytical strategies, and emerging biological insights. 46 studies used CyTOF alone, 12 employed IMC exclusively, and 3 combined both platforms. Median panel sizes were 33.5 markers for CyTOF and 33 for IMC. While lineage and immune checkpoint markers were universal, phospho-epitopes, metabolic enzymes, and stromal proteins appeared in more focused subsets. Most studies followed a three-step analytical workflow: (i) segmentation or gating, (ii) unsupervised clustering, and (iii) downstream spatial or functional analyses. CyTOF investigations frequently identified exhausted CD8 + T-cell subsets (e.g., PD-1 + TIM-3 + CD39 + ), suppressive myeloid populations (e.g., CD163 + HLA-DR - macrophages), and metabolically reprogrammed Tregs. IMC studies uncovered spatial patterns predictive of outcome, such as tertiary lymphoid structures (TLSs) and macrophage-T cell exclusion zones. Several studies proposed predictive immune signatures or integrated CyTOF with transcriptomic or spatial datasets. We identified five recurrent immunobiological motifs, CD8 + T-cell bifurcation, CD38 + TAM barriers, TLS maturity, CTLA-4 + NK-cell signatures and metabolically defined niches, highlighting convergent axes of resistance and response. Bioinformatic pipelines converged around FlowSOM or PhenoGraph clustering, CITRUS or elastic-net feature selection, and increasingly, machine learning and agent-based spatial modelling. Collectively, CyTOF and IMC are redefining biomarker discovery, therapeutic stratification, and virtual trial design in oncology, establishing high-dimensional CyTOF as a cornerstone of next-generation precision cancer medicine.

论文信息

作者
Vallée A、Drezet A、Arutkin M
第一作者单位
Department of Epidemiology and Public Health, Foch Hospital, Suresnes, France.France
通讯作者单位
School of Chemistry, Center for the Physics and Chemistry of Living Systems, Tel Aviv University, Tel Aviv-Yafo, Israel.Israel
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 41122166 · DOI 10.3389/fimmu.2025.1672312