TY - JOUR
T1 - Immune cell quantitation in normal breast tissue lobules with and without lobulitis
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
AU - Visscher, Daniel W.
N1 - Funding Information:
Acknowledgments This research was supported by a Grant from Susan G. Komen for the Cure®. Samples from the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center were used in this study. We thank contributors, including Indiana University, who collected samples used in this study, as well as donors and their families, whose help and participation made this work possible. Sincere thanks to Marilyn Churchward for assistance with manuscript preparation.
PY - 2014/4
Y1 - 2014/4
N2 - 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.
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.
KW - Breast lobules
KW - Cancer immunosuppression
KW - Immune cell
KW - Lobulitis
KW - Mucosal immunity
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U2 - 10.1007/s10549-014-2896-8
DO - 10.1007/s10549-014-2896-8
M3 - Article
C2 - 24596048
AN - SCOPUS:84899482563
SN - 0167-6806
VL - 144
SP - 539
EP - 549
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -