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, Beijing, 100021, P. R. China.
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, Beijing, 100021, P. R. China.
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, Beijing, 100021, P. R. China.
BGI Research, Shenzhen, 518083, P. R. China.
Institute of Intelligent Medical Research (IIMR), BGI Genomics, Shenzhen, 518083, P. R. China.
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
BGI Research, Sanya, 572025, P. R. China.
Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, P. R. China.
BGI Research, Sanya, 572025, P. R. China. yuezhen@genomics.cn.
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, Beijing, 100021, P. R. China. sunnan@cicams.ac.cn.
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, Beijing, 100021, P. R. China. sunnan@cicams.ac.cn.
BGI Research, Sanya, 572025, P. R. China. fangxd@genomics.cn.
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, Beijing, 100021, P. R. China. jmying@cicams.ac.cn.
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China. jmying@cicams.ac.cn.
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.
