德克萨斯大学研究团队报道了单细胞空间多组学揭示癌症相关成纤维细胞的保守空间亚型和细胞邻域。这一研究成果于2025年3月27日发表在国际顶尖学术期刊《癌细胞》上。

在这项研究中，通过7个空间转录组学和蛋白质组学平台对来自10种癌症类型的1400多万个细胞进行综合分析，课题组人员发现、验证并表征了不同的空间CAF亚型。这些亚型在不同的癌症类型中是保守的，并且独立于空间组学平台。值得注意的是，它们表现出独特的空间组织模式、邻近的细胞组成、相互作用网络和转录组谱。它们的丰度和组成因组织而异，形成TME特征，如肿瘤浸润免疫细胞的水平、分布和状态组成、肿瘤免疫表型和患者生存。这项研究丰富了他们对CAF在癌症中的空间异质性的理解，并为靶向和调节CAF的新方法铺平了道路。

据悉，癌症相关成纤维细胞（CAFs）是形成肿瘤微环境（TME）和影响治疗反应所必需的多面细胞群。表征复杂组织环境中CAFs的空间组织和相互作用为肿瘤生物学和免疫生物学提供了重要的见解。

附：英文原文

Title: Conserved spatial subtypes and cellular neighborhoods of cancer-associated fibroblasts revealed by single-cell spatial multi-omics

Author: Yunhe Liu, Ansam Sinjab, Jimin Min, Guangchun Han, Francesca Paradiso, Yuanyuan Zhang, Ruiping Wang, Guangsheng Pei, Yibo Dai, Yang Liu, Kyung Serk Cho, Enyu Dai, Akshay Basi, Jared K. Burks, Kimal I. Rajapakshe, Yanshuo Chu, Jiahui Jiang, Daiwei Zhang, Xinmiao Yan, Paola A. Guerrero, Alejandra Serrano, Mingyao Li, Tae Hyun Hwang, Andrew Futreal, Jaffer A. Ajani, Luisa M. Solis Soto, Amir A. Jazaeri, Humam Kadara, Anirban Maitra, Linghua Wang

Issue&Volume: 2025-03-27

Abstract: Cancer-associated fibroblasts (CAFs) are a multifaceted cell population essential for shaping the tumor microenvironment (TME) and influencing therapy responses. Characterizing the spatial organization and interactions of CAFs within complex tissue environments provides critical insights into tumor biology and immunobiology. In this study, through integrative analyses of over 14 million cells from 10 cancer types across 7 spatial transcriptomics and proteomics platforms, we discover, validate, and characterize four distinct spatial CAF subtypes. These subtypes are conserved across cancer types and independent of spatial omics platforms. Notably, they exhibit distinct spatial organizational patterns, neighboring cell compositions, interaction networks, and transcriptomic profiles. Their abundance and composition vary across tissues, shaping TME characteristics, such as levels, distribution, and state composition of tumor-infiltrating immune cells, tumor immune phenotypes, and patient survival. This study enriches our understanding of CAF spatial heterogeneity in cancer and paves the way for novel approaches to target and modulate CAFs.

DOI: 10.1016/j.ccell.2025.03.004

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00083-2