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Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation

Xin Wang, Zhanyu Wang, Qijun Liao, Pei Yuan, Junpu Mei, Yin Zhang, Chao Wu, Xiyu Kang, Sufei Zheng, Chenxuan Yang, Jiaxiang Liu, Qingyao Shang, Jiangtao Li, Bingning Wang, Liangyu Li, Hui Liu, Weining Hu, Zhensheng Dong, Jie Zhao, Linying Wang, Tao Liu, Yusheng Den, Chengrui Wang, Lijuan Han, Qianjun Chen, Huanming Yang, Xun Xu, Jie He, Zhen Yue (), Nan Sun (), Xiaodong Fang () and Jianming Ying ()
Additional contact information
Xin Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Zhanyu Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Qijun Liao: BGI Research
Pei Yuan: Chinese Academy of Medical Sciences and Peking Union Medical College
Junpu Mei: BGI Research
Yin Zhang: BGI Research
Chao Wu: BGI Research
Xiyu Kang: Chinese Academy of Medical Sciences and Peking Union Medical College
Sufei Zheng: Chinese Academy of Medical Sciences and Peking Union Medical College
Chenxuan Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Jiaxiang Liu: Chinese Academy of Medical Sciences and Peking Union Medical College
Qingyao Shang: Chinese Academy of Medical Sciences and Peking Union Medical College
Jiangtao Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Bingning Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Liangyu Li: BGI Research
Hui Liu: BGI Research
Weining Hu: BGI Research
Zhensheng Dong: BGI Research
Jie Zhao: BGI Research
Linying Wang: BGI Research
Tao Liu: BGI Research
Yusheng Den: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
Chengrui Wang: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
Lijuan Han: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
Qianjun Chen: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
Huanming Yang: BGI Research
Xun Xu: BGI Research
Jie He: Chinese Academy of Medical Sciences and Peking Union Medical College
Zhen Yue: BGI Research
Nan Sun: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaodong Fang: BGI Research
Jianming Ying: Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Breast cancers present intricate microenvironments comprising heterotypic cellular interactions, yet a comprehensive spatial map remained to be established. Here, we employed the DNA nanoball-based genome-wide in situ sequencing (Stereo-seq) to visualize the geospatial architecture of 30 primary breast tumors and metastatic lymph nodes across different molecular subtypes. This unprecedented high-resolution atlas unveils the fine structure of the tumor vasculature, highlighting heterogeneity in phenotype, spatial distribution, and intercellular communication within both endothelial and perivascular cells. In particular, venular smooth muscle cells are identified as the primary source of CCL21/CCL19 within the microenvironment. In collaboration with ACKR1-positive endothelial cells, they create a chemokine-rich venular niche to synergistically promote lymphocyte extravasation into tumors. High venule density predicts increased immune infiltration and improved clinical outcomes. This study provides a detailed spatial landscape of human breast cancer, offering key insights into the venular regulation of tumor immune infiltration.

Date: 2025
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DOI: 10.1038/s41467-025-58511-0

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