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

Amy C Degnim, Rushin D. Brahmbhatt, Derek C Radisky, Tanya L. Hoskin, Melody Stallings-Mann, Mark Laudenschlager, Aaron Mansfield, Marlene H. Frost, Linda Murphy, Keith L Knutson, Daniel W Visscher

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)539-549
Number of pages11
JournalBreast Cancer Research and Treatment
Volume144
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Breast
Dendritic Cells
Monocytes
Macrophages
T-Lymphocytes
Epithelium
Myeloid Cells
Helper-Inducer T-Lymphocytes
Immune System
Leukocytes
B-Lymphocytes
Cell Count
Lymphocytes
Breast Neoplasms

Keywords

  • Breast lobules
  • Cancer immunosuppression
  • Immune cell
  • Lobulitis
  • Mucosal immunity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Immune cell quantitation in normal breast tissue lobules with and without lobulitis. / Degnim, Amy C; Brahmbhatt, Rushin D.; Radisky, Derek C; Hoskin, Tanya L.; Stallings-Mann, Melody; Laudenschlager, Mark; Mansfield, Aaron; Frost, Marlene H.; Murphy, Linda; Knutson, Keith L; Visscher, Daniel W.

In: Breast Cancer Research and Treatment, Vol. 144, No. 3, 2014, p. 539-549.

Research output: Contribution to journalArticle

Degnim, Amy C ; Brahmbhatt, Rushin D. ; Radisky, Derek C ; Hoskin, Tanya L. ; Stallings-Mann, Melody ; Laudenschlager, Mark ; Mansfield, Aaron ; Frost, Marlene H. ; Murphy, Linda ; Knutson, Keith L ; Visscher, Daniel W. / Immune cell quantitation in normal breast tissue lobules with and without lobulitis. In: Breast Cancer Research and Treatment. 2014 ; Vol. 144, No. 3. pp. 539-549.
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AU - Degnim, Amy C

AU - Brahmbhatt, Rushin D.

AU - Radisky, Derek C

AU - Hoskin, Tanya L.

AU - Stallings-Mann, Melody

AU - Laudenschlager, Mark

AU - Mansfield, Aaron

AU - Frost, Marlene H.

AU - Murphy, Linda

AU - Knutson, Keith L

AU - Visscher, Daniel W

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AB - 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.

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