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Immune cell quantitation in normal breast tissue lobules with and without lobulitis
Amy C Degnim1, Rushin D Brahmbhatt, Derek C Radisky
1Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA, degnim.amy@mayo.edu.
Insights
Normal breast tissue contains immune cells, primarily within lobules. Lobules with inflammation show increased adaptive immune cells like B and T cells, indicating an active mucosal immune system.
Area of Science:
- Immunology
- Breast Biology
- Tissue Microenvironment
Background:
- The immune microenvironment is studied in breast cancer, but its role in normal breast tissue is poorly understood.
- Cellular immune components and their localization in non-malignant breast tissue require further investigation.
Purpose of the Study:
- To quantify and localize cellular immune components within normal breast lobules.
- To compare immune cell densities in lobules with and without visible immune infiltrates (lobulitis).
Main Methods:
- Analysis of 11 normal breast tissue samples, assessing up to ten lobules per sample.
- Quantification of B cells (CD20), cytotoxic T cells (CD8), helper T cells (CD4), dendritic cells (CD11c), leukocytes (CD45), and monocytes/macrophages (CD68) using digital image analysis.
- Comparison of immune cell densities between lobules with and without lobulitis.
Main Results:
- Immune cells were predominantly localized to lobules, not stroma, in all normal samples.
- Most lobules contained CD8+, CD11c+, CD45+, and CD68+ cells, with fewer CD4+ and CD20+ cells.
- Lobules with lobulitis exhibited significantly higher densities of CD4+, CD8+, CD20+, and CD45+ cells, but not monocytes/macrophages or dendritic cells.
- Cytotoxic T cells (CD8+) and dendritic cells (CD11c+) were closely associated with the lobule epithelium.
Conclusions:
- Normal breast tissue harbors a dynamic mucosal immune system with myeloid and lymphoid cells localized to lobules.
- Lobulitis in normal breast tissue is associated with an increase in adaptive immune cells (B and T cells).
- These findings highlight the immune activity present even in non-malignant breast tissue.
Abstract:
While the immune microenvironment has been investigated in breast cancers, little is known about its role in non-malignant breast tissues. Here we quantify and localize cellular immune components in normal breast tissue lobules, with and without visible immune infiltrates (lobulitis). Up to ten representative lobules each in eleven normal breast tissue samples were assessed for B cells (CD20), cytotoxic T cells (CD8), helper T cells (CD4), dendritic cells (CD11c), leukocytes (CD45), and monocytes/macrophages (CD68). Using digital image analysis, immune cell densities were measured and compared between lobules with/without lobulitis. 109 lobules in 11 normal breast tissue samples were evaluated; 31 with lobulitis and 78 without. Immune cells showed consistent patterns in all normal samples, predominantly localized to lobules rather than stroma. Regardless of lobulitis status, most lobules demonstrated CD8+, CD11c+, CD45+, and CD68+ cells, with lower densities of CD4+ and CD20+ cells. Both CD11c+ and CD8+ cells were consistently and intimately associated with the basal aspect of lobule epithelium. Significantly higher densities of CD4+, CD8+, CD20+, and CD45+ cells were observed in lobules with lobulitis. In contrast, densities of monocytes/macrophages and dendritic cells did not vary with lobulitis. In normal breast tissue, myeloid and lymphoid cells are present and localized to lobules, with cytotoxic T and dendritic cells directly integrated with epithelium. Lobules with lobulitis have significantly more adaptive immune (B and T) cells, but no increase in dendritic cells or monocytes/macrophages. These findings indicate an active and dynamic mucosal immune system in normal breast tissue.
