Preclinical study

Breast Cancer Research and Treatment

, Volume 144, Issue 3, pp 539-549

Open Access This content is freely available online to anyone, anywhere at any time.

Immune cell quantitation in normal breast tissue lobules with and without lobulitis

  • Amy C. DegnimAffiliated withDepartment of Surgery, Mayo Clinic Email author 
  • , Rushin D. BrahmbhattAffiliated withDepartment of Surgery, Mayo Clinic
  • , Derek C. RadiskyAffiliated withDepartment of Biochemistry and Molecular Biology, Mayo Clinic Florida
  • , Tanya L. HoskinAffiliated withDivision of Biomedical Statistics and Informatics, Mayo Clinic
  • , Melody Stallings-MannAffiliated withDepartment of Biochemistry and Molecular Biology, Mayo Clinic Florida
  • , Mark LaudenschlagerAffiliated withDepartment of Laboratory Medicine and Pathology, Mayo Clinic
  • , Aaron MansfieldAffiliated withDivision of Medical Oncology, Mayo Clinic
  • , Marlene H. FrostAffiliated withWomen’s Cancer Program, Mayo Clinic
  • , Linda MurphyAffiliated withWomen’s Cancer Program, Mayo Clinic
    • , Keith KnutsonAffiliated withDepartment of Immunology, Mayo Clinic
    • , Daniel W. VisscherAffiliated withDepartment of Laboratory Medicine and Pathology, Mayo Clinic

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.

Keywords

Immune cell Breast lobules Lobulitis Mucosal immunity Cancer immunosuppression