Estrogen-induced immune changes within the normal mammary gland

Area of Science:

• Immunology
• Endocrinology
• Oncology

Background:

• Aberrant hormone exposure is linked to increased breast cancer (BCa) incidence, particularly in estrogen receptor (ER) + positive mammary epithelium.
• Estrogen exposure during mammary involution can drive tumor growth via neutrophils.
• The role of the ER + immune microenvironment in mediating hormonally controlled BCa risk during normal development is not fully understood.

Purpose of the Study:

• To investigate the impact of hormonal manipulation on the immune cell microenvironment in the context of BCa risk.
• To determine how estrogen and its inhibition affect innate and adaptive immune cell populations in mammary tissue.

Main Methods:

• Tumor-naive mice were treated with oophorectomy, estrogen (17β estradiol), or Fulvestrant.
• Mammary tissue, lymph nodes, and blood were collected for analysis.
• Flow cytometry was employed to quantify changes in innate and adaptive immune cell frequencies.

Main Results:

• Oophorectomy and Fulvestrant decreased pro-tumor M2 macrophages and neutrophils, while increasing dendritic cells and eosinophils in mammary tissue.
• Estrogen increased M2 macrophages, regulatory T cells, and decreased cytotoxic CD8 + T cells and B cells.
• Immune cell changes, except for eosinophils, were primarily observed in mammary tissue.

Conclusions:

• Inhibiting estrogen action reduces immunosuppressive myeloid cells and enhances antigen presentation and cytotoxic effects.
• Estrogen exposure increases immunosuppressive cells and decreases anti-tumor T cells, potentially contributing to BCa risk.
• Hormonal influences on BCa risk may be partly mediated by modulation of the immune microenvironment.