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Related Experiment Video

Updated: Feb 7, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
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Distinct Endothelial Phenotype Associates with Macrophage-Enriched Microenvironments in Triple-Negative Breast

Luis Becerra-Dominguez1,2,3,4, Liqun Yu1,2,3, Charlotte Helena Rivas1,2,3,5

  • 1Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.

Research Square
|February 6, 2026
PubMed
Summary

Macrophages influence blood vessel structure in triple-negative breast cancer (TNBC), promoting vascular normalization in macrophage-rich tumors. This immune-vascular crosstalk impacts drug delivery and therapeutic resistance in TNBC.

Keywords:
Endothelial CellsMacrophagesTriple-Negative Breast CancerTumor MicroenvironmentVascular Normalization

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Area of Science:

  • Oncology
  • Immunology
  • Vascular Biology

Background:

  • Triple-negative breast cancer (TNBC) is aggressive with few treatments due to heterogeneity.
  • Tumor vasculature significantly impacts TNBC progression and therapeutic resistance.
  • Macrophage abundance is a key factor influencing the tumor microenvironment.

Purpose of the Study:

  • To investigate the relationship between macrophage abundance and tumor vasculature in TNBC.
  • To identify how macrophage-driven changes in vasculature affect endothelial cell states.
  • To explore the conservation of these immune-vascular dynamics in human TNBC.

Main Methods:

  • Utilized murine TNBC models with varying macrophage levels.
  • Assessed tumor vasculature through pericyte coverage and lectin perfusion.
  • Performed single-cell RNA sequencing on endothelial cells.
  • Analyzed human TNBC single-cell datasets for endothelial and immune cell composition.

Main Results:

  • Macrophage-enriched tumors showed vascular normalization (increased pericyte coverage, perfusion).
  • Endothelial cells in macrophage-rich tumors upregulated inflammatory and venous-like genes.
  • Macrophage-poor tumors exhibited arterial, lymphatic, and homeostatic endothelial profiles.
  • Human TNBC data confirmed macrophage abundance correlates with immunologically active endothelium.

Conclusions:

  • Macrophage abundance is conservedly associated with specific vascular states in TNBC.
  • Immune-vascular dynamics, particularly macrophage-endothelial cell interactions, are crucial in TNBC.
  • Targeting these interactions may offer novel therapeutic strategies for TNBC.