Deciphering the Cellular and Metabolic Landscape of Lymph Node Metastasis in Breast Cancer Using Single-Cell and...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Metastasis is a critical challenge in breast cancer (BRCA), with lymph node (LN) involvement being common.
• The cellular and molecular mechanisms driving LN metastasis are not fully understood.

Purpose of the Study:

• To create a detailed single-cell atlas of metastatic niches in BRCA.
• To elucidate the cellular composition, signaling networks, and molecular drivers of LN metastasis.
• To identify potential therapeutic targets for metastatic breast cancer.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of 78 primary breast tumors and paired LN metastases.
• Identification of early-disseminated cancer cells (EDCs) and their characteristics.
• Analysis of intercellular communication networks within the metastatic microenvironment.
• Computational drug repositioning to identify potential therapies.
• Validation using spatial transcriptomics (ST) data.

Main Results:

• Distinct epithelial cell subpopulations, including EDCs, were identified.
• Significant metabolic reprogramming and immune modulation were observed in malignant epithelial cells.
• A communication network involving lymphocytes, macrophages, and epithelial cells was delineated, promoting an immunosuppressive microenvironment.
• Four tyrosine kinase receptor inhibitors were identified as potential therapeutic agents.

Conclusions:

• The study provides a comprehensive cellular and molecular understanding of LN metastasis in BRCA.
• Metabolic reprogramming and immune modulation are key features of metastatic progression.
• Targeting identified crosstalk pathways may offer novel therapeutic strategies for metastatic breast cancer.