Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation
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.
Authors
- Chao Wu (ORCID: https://orcid.org/0000-0002-2219-5203)
- Jianming Ying (ORCID: https://orcid.org/0000-0003-2692-4052)
- Huanming Yang (ORCID: https://orcid.org/0000-0002-0858-3410)
- Qijun Liao (ORCID: https://orcid.org/0000-0001-7517-9867)
- Yusheng Den
- Weining Hu (ORCID: https://orcid.org/0000-0002-5153-2328)
- Junpu Mei (ORCID: https://orcid.org/0000-0003-4630-0765)
- Qingyao Shang
- Chengrui Wang (ORCID: https://orcid.org/0000-0003-0618-0797)
- Xiaodong Fang (ORCID: https://orcid.org/0000-0001-7061-3337)
- Tao Liu (ORCID: https://orcid.org/0000-0002-1482-4858)
- Bingning Wang (ORCID: https://orcid.org/0000-0003-4095-5082)
- Zhen Yue (ORCID: https://orcid.org/0000-0001-6993-6067)
- Sufei Zheng
- Chenxuan Yang (ORCID: https://orcid.org/0000-0001-9064-9740)
- Liangyu Li (ORCID: https://orcid.org/0000-0002-3540-7551)
- Nan Sun (ORCID: https://orcid.org/0000-0001-6812-9917)
- Xin Wang (ORCID: https://orcid.org/0000-0003-1753-2786)
- Hui Liu (ORCID: https://orcid.org/0000-0002-7669-9386)
- Jiangtao Li (ORCID: https://orcid.org/0000-0001-6860-6103)
- Xun Xu (ORCID: https://orcid.org/0000-0002-5338-5173)
- Yin Zhang
- Zhanyu Wang (ORCID: https://orcid.org/0000-0001-9187-6419)
- Jie He (ORCID: https://orcid.org/0000-0002-0285-5403)
- Pei Yuan
- Zhensheng Dong
- Lijuan Han (ORCID: https://orcid.org/0000-0002-7401-0506)
- Linying Wang (ORCID: https://orcid.org/0000-0001-8023-0823)
- Jie Zhao (ORCID: https://orcid.org/0009-0001-3796-4503)
- Qianjun Chen (ORCID: https://orcid.org/0000-0001-6761-7740)
- Jiaxiang Liu
- Xiyu Kang
Institutions
- BGI Group (China) (CN)
- Guangzhou University of Chinese Medicine (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- National Cancer Center (US)
- Sanya University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1038/s41467-025-58511-0
- Citations
- 11
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 8.87
Funders
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- Government of Guangdong Province
- Natural Science Foundation of Beijing Municipality
- Chinese Academy of Medical Sciences
- Beijing Municipal Science and Technology Commission
- National Science and Technology Major Project