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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Dissecting the Non-Immune Tumor Microenvironment in Triple-Negative Breast Cancer: Molecular Subtype-Specific

Antonia Syrnioti1, Eleni Timotheadou2, Vasileios Papadopoulos3

  • 1Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

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|November 27, 2025
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Summary

Triple-Negative Breast Cancer (TNBC) exhibits diverse molecular subtypes. Differences in their non-immune tumor microenvironment, including fibroblasts and extracellular matrix, may impact prognosis and guide personalized therapies.

Keywords:
angiogenesiscancer-associated fibroblastsepithelial–mesenchymal transitionextracellular matrixgene expressionhistologyhypoxiaimmunohistochemistrymetabolic reprogrammingprogression

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Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment Research

Background:

  • Triple-Negative Breast Cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes (BL1, BL2, IM, M, MSL, LAR).
  • While immune aspects of TNBC subtypes are known, non-immune stromal components are under-recognized.
  • Understanding the non-immune microenvironment is crucial for TNBC biology.

Purpose of the Study:

  • To review and synthesize evidence on non-immune microenvironmental differences across TNBC molecular subtypes.
  • To focus on cancer-associated fibroblasts (CAFs), vascularity, extracellular matrix (ECM), epithelial-mesenchymal transition (EMT), and metabolic reprogramming.
  • To highlight subtype-specific signatures and their potential clinical significance.

Main Methods:

  • Narrative review of existing scientific literature.
  • Integration of data from multiple studies on TNBC molecular subtypes.
  • Focus on non-immune stromal and structural components of the tumor microenvironment.

Main Results:

  • Significant differences exist in the non-immune microenvironment across TNBC molecular subtypes.
  • Key components examined include CAFs, vascular features, ECM dynamics, EMT, and metabolic-hypoxic reprogramming.
  • Subtype-specific signatures in stromal architecture and metabolic adaptations were identified.

Conclusions:

  • The non-immune microenvironment varies significantly between TNBC molecular subtypes.
  • These variations may have prognostic and predictive value.
  • Targeting the tumor-stroma interface offers potential for personalized therapeutic strategies in TNBC.