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Updated: May 10, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Mechanisms of tumor immune escape in triple-negative breast cancers (TNBC) with and without mutated BRCA 1
Jörg B Engel1, Arnd Honig, Michaela Kapp
1Universitätsfrauenklinik Regensburg, Caritas Krankenhaus St Josef, Landshuter Str 65, 93053, Regensburg, Germany, joergbengel@hotmail.com.
Purpose:
Triple negative breast cancers (TNBC) are associated with an adverse outcome, although these tumors are sensitive to chemotherapy. In part, this phenomenon could be caused by tumor immune escape. The current study investigates immunogenicity of TNBC cells in vitro and the presence of immunosuppressive factors in the tumor microenvironment (pAKT and B7H1 expression, infiltration with regulatory T cells, [Tregs]).
Methods:
Natural killer (NK)-cell induced lysis was evaluated in estrogen receptor (ER) positive MCF 7 breast cancers, in MDA-MB231 and MDA-MB468 and in HCC-1937 (BRCA 1 mutated) and HCC-1806 TNBC cells. Expression of pAKT, B7H1 and infiltration with Tregs were determined by immunohistochemistry in human specimens of benign and malignant breast disease.
Results:
NK-cell induced lysis was significantly increased (p < 0.05) in four TNBC cell lines compared to ER + MCF 7 cells. Fibroadenomas and mastectomy samples were not infiltrated with Tregs. Infiltration with Tregs was 0.92 ± 0.21 in ER/PR + breast cancers and significantly higher in TNBC without (2.30 ± 0.34) and also significantly higher with mutation of BRCA 1 (2.10 ± 0.34). Expression of pAKT was absent in benign controls and 1.23 ± 0.36 in ER/PR + breast cancers, 1.78 ± 0.40 in TNBC without and 2.40 ± 0.30 with mutated BRCA 1. No significant differences of B7H1 expression occurred among the breast cancer subgroups.
Conclusion:
TNBC cell stimulate the NK-cell immune response significantly stronger than ER positive breast cancer cells. This could explain why infiltration with immunosuppressive Tregs is increased in human specimens of TNBC with and without mutated BRCA 1. Accordingly, immunomodulatory treatment strategies should be further explored in TNBC.
Insights
Triple negative breast cancer (TNBC) cells show stronger NK-cell immune response than ER-positive cells. Increased regulatory T cells (Tregs) in TNBC may explain immune escape, suggesting immunomodulatory treatments for TNBC.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Triple negative breast cancer (TNBC) presents an adverse prognosis despite chemotherapy sensitivity.
- Tumor immune escape is a potential mechanism contributing to TNBC's poor outcome.
- Investigating TNBC immunogenicity and the tumor microenvironment's immunosuppressive factors is crucial.
Purpose of the Study:
- To evaluate the immunogenicity of TNBC cells in vitro.
- To assess the presence of immunosuppressive factors, including pAKT and B7H1 expression and regulatory T cell (Treg) infiltration, within the TNBC tumor microenvironment.
Main Methods:
- NK-cell induced lysis was assessed in various TNBC cell lines (MDA-MB231, MDA-MB468, HCC-1937, HCC-1806) and compared to ER-positive MCF 7 cells.
- Immunohistochemistry was used to determine pAKT, B7H1 expression, and Treg infiltration in human breast tissue specimens.
Main Results:
- TNBC cell lines exhibited significantly increased NK-cell induced lysis compared to ER-positive MCF 7 cells.
- Treg infiltration was significantly higher in TNBC specimens (with and without BRCA 1 mutation) compared to benign controls and ER/PR-positive breast cancers.
- pAKT expression was elevated in TNBC, particularly in those with BRCA 1 mutations, while B7H1 expression showed no significant differences across subgroups.
Conclusions:
- TNBC cells elicit a stronger NK-cell immune response than ER-positive breast cancer cells.
- Increased Treg infiltration in TNBC correlates with elevated pAKT, potentially contributing to immune suppression.
- Further exploration of immunomodulatory treatment strategies is warranted for TNBC management.
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