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Published on: December 6, 2014
Histological Analysis of γδ T Lymphocytes Infiltrating Human Triple-Negative Breast Carcinomas
Jose Villacorta Hidalgo1, Peter Bronsert2, Marzenna Orlowska-Volk3
1Department of Pathology, University of Freiburg Medical Center , Freiburg im Breisgau , Germany ; Faculty of Biology, University of Freiburg , Freiburg im Breisgau , Germany ; University Hospital "José de San Martin", University of Buenos Aires , Buenos Aires , Argentina.
Abstract:
Breast cancer is the leading cause of cancer death in women and the second most common cancer worldwide after lung cancer. The remarkable heterogeneity of breast cancers influences numerous diagnostic, therapeutic, and prognostic factors. Triple-negative breast carcinomas (TNBCs) lack expression of HER2 and the estrogen and progesterone receptors and often contain lymphocytic infiltrates. Most of TNBCs are invasive ductal carcinomas (IDCs) with poor prognosis, whereas prognostically more favorable subtypes such as medullary breast carcinomas (MBCs) are somewhat less frequent. Infiltrating T-cells have been associated with an improved clinical outcome in TNBCs. The prognostic role of γδ T-cells within CD3(+) tumor-infiltrating T lymphocytes remains unclear. We analyzed 26 TNBCs, 14 IDCs, and 12 MBCs, using immunohistochemistry for the quantity and patterns of γδ T-cell infiltrates within the tumor microenvironment. In both types of TNBCs, we found higher numbers of γδ T-cells in comparison with normal breast tissues and fibroadenomas. The numbers of infiltrating γδ T-cells were higher in MBCs than in IDCs. γδ T-cells in MBCs were frequently located in direct contact with tumor cells, within the tumor and at its invasive border. In contrast, most γδ T-cells in IDCs were found in clusters within the tumor stroma. These findings could be associated with the fact that the patient's prognosis in MBCs is better than that in IDCs. Further studies to characterize these γδ T-cells at the molecular and functional level are in progress.
Insights
Triple-negative breast cancer (TNBC) subtypes show distinct patterns of gamma-delta T-cell infiltration. Medullary breast carcinomas (MBCs) have more gamma-delta T-cells than invasive ductal carcinomas (IDCs), potentially explaining better prognoses.
Area of Science:
- Immunology
- Oncology
- Pathology
Background:
- Breast cancer is a leading cause of cancer death globally, with significant heterogeneity impacting prognosis.
- Triple-negative breast carcinomas (TNBCs) are aggressive, lacking key receptor expression and often associated with poor outcomes.
- Tumor-infiltrating T-cells, particularly gamma-delta (γδ) T-cells, are implicated in TNBC, but their prognostic role is unclear.
Purpose of the Study:
- To investigate the quantity and spatial distribution of γδ T-cells within the tumor microenvironment of different TNBC subtypes.
- To compare γδ T-cell infiltrates in medullary breast carcinomas (MBCs) and invasive ductal carcinomas (IDCs), both subtypes of TNBC.
- To explore potential associations between γδ T-cell patterns and the known prognostic differences between MBCs and IDCs.
Main Methods:
- Analysis of 26 TNBC samples, including 14 IDCs and 12 MBCs.
- Immunohistochemistry was employed to quantify and characterize the patterns of γδ T-cell infiltration.
- Comparison of γδ T-cell infiltrates in tumor tissues versus normal breast tissues and fibroadenomas.
Main Results:
- Both TNBC subtypes (IDCs and MBCs) exhibited higher numbers of γδ T-cells compared to normal breast tissues and fibroadenomas.
- Medullary breast carcinomas (MBCs) demonstrated significantly higher numbers of infiltrating γδ T-cells than invasive ductal carcinomas (IDCs).
- γδ T-cells in MBCs were often found in direct contact with tumor cells, whereas in IDCs, they were predominantly located in stromal clusters.
Conclusions:
- Distinct patterns of γδ T-cell infiltration exist between MBCs and IDCs, suggesting subtype-specific immune responses.
- The higher infiltration and direct tumor cell contact of γδ T-cells in MBCs may contribute to their more favorable prognosis compared to IDCs.
- Further molecular and functional characterization of these γδ T-cells is warranted to elucidate their precise role in TNBC.
