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

2025.04.09

Paper Review:


Breast cancer remains one of the most prevalent and deadly cancers globally, with its diverse molecular subtypes posing significant treatment challenges. In recent years, the combination therapy of immune checkpoint inhibitors (ICIs) and chemotherapy has achieved certain progress in treating triple-negative breast cancer, but its efficacy remains limited in patients with other molecular subtypes. The primary obstacle is insufficient immune cell infiltration into the tumor microenvironment (TME), a critical factor for immunotherapy success.

A new study titled "Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation", published in Nature Communications, uses Stereo-seq spatial transcriptomics technology to create a high-resolution spatial map of the breast cancer tumor environment. The research analyzed 30 surgically resected primary breast tumors and paired lymph node metastases from 23 patients, covering various molecular subtypes. It identifies a "chemokine-rich venular niche" within the tumor vasculature. Venular smooth muscle cells (vSMCs) produce chemokines CCL21 and CCL19, which, in collaboration with ACKR1-positive venular endothelial cells (vECs), attract and guide CCR7+ lymphocytes into the tumor, facilitating their extravasation. The findings provide unprecedented insights into the tumor vasculature and its role in immune infiltration. By understanding how immune cells access tumors, this research opens the door to new treatments that could make immunotherapy work for more patients.

By using Stereo-seq, the research provides the first high-resolution spatial map of the breast cancer TME. Unlike "conventional ST methods, such as Visium, exhibit insufficient resolution due to their reliance on 55μm barcoded spots, with a center-to-center distance of 100μm, that encompass dozens of cells, thus impeding precise localization of dispersed ECs and perivascular cells within the TME.” "An innovative technology, SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), has recently been developed that combines 220 nm DNA nanoball (DNB)- patterned arrays and in situ tissue RNA capture to create spatial maps at cellular resolution, making it an ideal tool to depict the intricate tumor vasculature.”

Learn more about the study:
https://doi.org/10.1038/s41467-025-58511-0

About STOmics Stereo-seq:
STOmics offers the most advanced spatiotemporal multi-omics technology, enabling unbiased discovery to answer biological questions in scientific research and clinical applications. Currently, we offer spatial transcriptomics solutions, including Stereo-seq v1.3 for fresh frozen samples, Stereo-seq OMNI for FFPE samples, Stereo-seq Large Chip Designs (LCD) for centimeter-level fresh frozen samples (now up to 2cm x 3cm), and a spatial multi-omics solution - Stereo-CITE for high-plex spatial proteo-transcriptome co-detection.
https://en.stomics.tech/

Nature Communications Species·human Organ/Tissue·30 primary breast tumors and metastatic lymph nodes across different molecular subtypes