哈佛医学院Peter K. Sorger小组研制了人类肿瘤细胞状态和免疫生态位的高度多重3D分析。相关论文于2025年9月29日发表在《自然—方法学》杂志上。

在这里，该课题组研究人员描述了一种用于三维组织成像的高plex循环免疫荧光方法，并展示了在常规薄组织切片中很少（如果有的话）细胞是完整的，从而降低了细胞表型和相互作用分析的准确性。

然而，厚8至10倍切片的三维循环免疫荧光能够准确地评估完整肿瘤、免疫细胞和基质细胞中的各种蛋白质标记物。

此外，这种共聚焦方法的高分辨率产生的细胞图像在一个保存的组织环境中的细节水平，以前仅限于细胞培养。细胞膜的精确成像也使得检测和绘制免疫细胞壁龛中的细胞接触和近线信号复合物成为可能。

据介绍，癌症等疾病涉及细胞比例、状态和相互作用的改变，以及组织形态和结构的复杂变化。疾病的组织病理学诊断和大多数多重空间分析依赖于检查薄层(4-5 μm)标本。

附：英文原文

Title: Highly multiplexed 3D profiling of cell states and immune niches in human tumors

Author: Yapp, Clarence, Nirmal, Ajit J., Zhou, Felix, Wong, Alex Y. H., Tefft, Juliann B., Lu, Yi Daniel, Shang, Zhiguo, Maliga, Zoltan, Llopis, Paula Montero, Murphy, George F., Lian, Christine G., Danuser, Gaudenz, Santagata, Sandro, Sorger, Peter K.

Issue&Volume: 2025-09-29

Abstract: Diseases such as cancer involve alterations in cell proportions, states and interactions, as well as complex changes in tissue morphology and architecture. Histopathological diagnosis of disease and most multiplexed spatial profiling relies on inspecting thin (4–5μm) specimens. Here we describe a high-plex cyclic immunofluorescence method for three-dimensional tissue imaging and use it to show that few, if any, cells are intact in conventional thin tissue sections, reducing the accuracy of cell phenotyping and interaction analysis. However, three-dimensional cyclic immunofluorescence of sections eightfold to tenfold thicker enables accurate morphological assessment of diverse protein markers in intact tumor, immune and stromal cells. Moreover, the high resolution of this confocal approach generates images of cells in a preserved tissue environment at a level of detail previously limited to cell culture. Precise imaging of cell membranes also makes it possible to detect and map cell–cell contacts and juxtracrine signaling complexes in immune cell niches.

DOI: 10.1038/s41592-025-02824-x

Source: https://www.nature.com/articles/s41592-025-02824-x