Histological Analysis of γδ T Lymphocytes Infiltrating Human Triple-Negative Breast Carcinomas

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.

In the Absence of a TCR Signal IL-2/IL-12/18-Stimulated γδ T Cells Demonstrate Potent Anti-Tumoral Function Through Direct Killing and Senescence Induction in Cancer Cells

“…γδ T cells infiltrate a variety of cancers and modulate anti-tumor immunity [41][42][43][44], and a recent extensive gene expression study identified tumor-infiltrating γδ T cells as the most favorable prognostic marker in many types of cancer [45]. Along with their unique beneficial features such as the production of abundant pro-inflammatory cytokines, including IFN-γ and TNF-α, MHC-independent recognition of antigens, direct lysis of tumor cells, antibody-dependent cellular cytotoxicity (ADCC), and antigen presentation capacity [46], γδ T cells are proposed to constitute a promising target in cancer immunotherapy.…”

The role of gamma delta T lymphocytes in breast cancer: a review

“…In a small study, which focussed on triple negative breast cancer, Hidalgo and coworkers demonstrated that the lymphocytic infiltrate of these tumours contained many γδT lymphocytes, compared to normal breast tissue. They compared ductal and medullary breast cancer tissue and found differences in the distribution of γδT lymphocytes between the two tumour types; they were more frequently located in the stroma of the ductal specimens whereas they were more typically located in the tumour parenchyma and at the invasive tumour cell margin of medullary tumours (42). independent of receptor status, and improved overall survival in the HER2 positive subtype (HR 0.27; 95% CI:0.10-0.73; p=0.009).…”

Identification of a tumor-specific allo-HLA–restricted γδTCR

“…3 Recently, the important biological role of gdT cells in cancer immune surveillance has been further highlighted by the fact that gdT cells infiltrate various tumors. 4,5 However, the biological understanding of cancer immune surveillance and potential clinical applicability of gdT cells, or their individual receptors, is substantially hampered by the lack of well-defined gdT-cell receptor (TCR) ligands, as well as their precise molecular requirements for recognition. 6 gdT-cell ligands that have been identified so far are mostly associated with metabolic changes in stressed cells.…”