Profiling of the TNBC Tumor Microenvironment's Functional Heterogeneity by CITE-seq to Guide Personalized Medicine

Area of Science:

• Immunology
• Oncology
• Single-cell genomics

Background:

• Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
• The tumor microenvironment (TME) in TNBC is complex and heterogeneous.
• Resistance to immune checkpoint inhibitors is common in TNBC.

Purpose of the Study:

• To deconstruct the TNBC immune ecosystem.
• To generate a comprehensive cellular atlas of the TNBC tumor microenvironment.
• To identify potential therapeutic targets within the TNBC TME.

Main Methods:

• Applied CITE-seq to 2,356 murine TNBC cells.
• Performed batch correction and cell clustering.
• Focused sub-clustering on tumor-associated macrophages (TAMs) and T cells for functional analysis.

Main Results:

• Resolved six primary cell populations in the TNBC TME.
• Identified three distinct TAM subpopulations: antigen-presenting, metabolically active, and erythrophagocytic.
• Characterized five major T-cell states and identified potential therapeutic targets.

Conclusions:

• Revealed significant functional diversity in TNBC immune cells, especially TAMs and T cells.
• Highlighted metabolically specialized and erythrophagocytic TAMs.
• Provided a foundation for precision medicine in TNBC through a detailed immune cell atlas and identified drug targets.