Nature Communications (Apr 2025)
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,
- Jianming Ying
Affiliations
- Xin Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Zhanyu Wang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Qijun Liao
- BGI Research
- Pei Yuan
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Junpu Mei
- BGI Research
- Yin Zhang
- BGI Research
- Chao Wu
- BGI Research
- Xiyu Kang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Sufei Zheng
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Chenxuan Yang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Jiaxiang Liu
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Qingyao Shang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Jiangtao Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Bingning Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, 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
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
- Chengrui Wang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
- Lijuan Han
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
- Qianjun Chen
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
- Huanming Yang
- BGI Research
- Xun Xu
- BGI Research
- Jie He
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Zhen Yue
- BGI Research
- Nan Sun
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Xiaodong Fang
- BGI Research
- Jianming Ying
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- DOI
- https://doi.org/10.1038/s41467-025-58511-0
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 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.
