PO.TB10.08 · 肿瘤生物学
具有超过100种生物标志物的自动化多组学检测用于多种癌症类型肿瘤微环境的深入空间分析
Automated multiomics assay with over 100 biomarkers for in-depth spatial profiling of the tumor microenvironment in multiple cancer types
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摘要 Abstract
中文摘要
背景
肿瘤微环境（TME）在癌症进展、免疫逃逸和治疗反应中发挥关键作用。理解TME内细胞的空间组织和功能状态对于推进免疫肿瘤学和精准医学至关重要[PMID: 40102282]。然而，在原位同时可视化分泌分子和细胞表型仍是空间生物学领域的一项重大挑战[PMID: 39930476]。在此，我们采用自动化超多重（hyperplex）多组学检测同时检测RNA和蛋白表达，以在空间上绘制多种癌症类型TME中的细胞表型及其功能状态。
方法
我们检查了由多种人类癌症类型组成的福尔马林固定石蜡包埋组织芯片（TMA）：前列腺癌、肺癌、乳腺癌、结直肠癌、黑色素瘤和淋巴瘤。TMA切片在COMET™平台上进行染色和成像，整合RNAscope™ HiPlex Pro进行转录本检测和序贯免疫荧光（seqIF™）进行蛋白质组分析[PMID: 22166544; 37813886; 41065276]。使用HORIZON™软件分析图像以提取单细胞和空间特征。
结果
该自动化多组学方法实现了在同一切片上同时原位检测超过100个生物分子靶标，包括12个转录本和90个以上的蛋白。TME的高分辨率空间分析实现了对癌细胞、间质、血管和多样免疫细胞亚群的准确定位。它进一步揭示了与肿瘤抑制或原癌基因活性相关的关键分子特征，包括增殖、凋亡和免疫检查点调控的标志物。同时检测细胞因子和趋化因子转录本突显了肿瘤和间质区室内的局部免疫信号传导及细胞间通讯。
结论
该多组学工作流程为跨多种癌症类型深入表征TME提供了强大工具，同时显著减少样本消耗。空间分析为剖析组织结构和免疫动态、识别可用于免疫治疗和个性化医学的功能细胞状态及相互作用提供了新机遇。
查看英文原文 English abstract
Background
The tumor microenvironment (TME) plays a pivotal role in cancer progression, immune evasion, and therapeutic response. Understanding the spatial organization and functional states of cells within the TME is essential for advancing immuno-oncology and precision medicine [PMID: 40102282]. However, simultaneous visualization of secreted molecules and cellular phenotypes in situ remains a major challenge in the spatial biology field [PMID: 39930476]. Here, we employed an automated hyperplex multiomics assay to simultaneously detect RNA and protein expressions to spatially map cell phenotypes and their functional states in the TME of multiple cancer types.
Methods
We examined a formalin-fixed paraffin-embedded tissue microarray (TMA) comprising various human cancer types: prostate, lung, breast, colorectal, melanoma, and lymphoma. A TMA section was stained and imaged on the COMET™ platform, integrating RNAscope™ HiPlex Pro for transcript detection and sequential immunofluorescence (seqIF™) for proteomic analysis [PMID: 22166544; 37813886; 41065276]. Image was analyzed using HORIZON™ software to extract single-cell and spatial features.
Results
The automated multiomics approach enabled the concomitant in situ detection of over 100 biomolecular targets, including 12 transcripts and more than 90 proteins on the same section. High-resolution spatial profiling of the TME allowed accurate mapping of cancer, stromal, vascular and diverse immune cell subsets. It further revealed key molecular features associated with tumor-suppressor or proto-oncogene activity, including markers of proliferation, apoptosis, and immune checkpoint regulation. Concurrent detection of cytokine and chemokine transcripts highlighted localized immune signaling and cell-cell communication within tumor and stromal compartments.
Conclusions
This multiomics workflow offers a powerful tool for in-depth characterization of the TME across multiple cancer types, while significantly reducing sample consumption. Spatial profiling provides new opportunities to dissect the tissue architecture and immune dynamics to identify functional cell states and interactions to be exploited in immunotherapy and personalized medicine.
利益披露 Disclosure
M. Bonnet, None..
C. Saygili-Demir, None..
K. Handel, None..
P. Machado, None..
A. Failletaz, None..
D. Wakhloo, None..
A. Dikshit, None..
M. Procopio, None..
S. Brajkovic, None.