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, Visscher Daniel W
Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA,
Breast Cancer Res Treat. 2014 Apr;144(3):539-49. doi: 10.1007/s10549-014-2896-8. Epub 2014 Mar 5.
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.
虽然已经对乳腺癌中的免疫微环境进行了研究，但对其在非恶性乳腺组织中的作用却知之甚少。在此，我们对正常乳腺组织小叶中的细胞免疫成分进行定量和定位，这些小叶有或没有明显的免疫浸润（小叶炎）。对11个正常乳腺组织样本中每个样本多达10个代表性小叶进行B细胞（CD20）、细胞毒性T细胞（CD8）、辅助性T细胞（CD4）、树突状细胞（CD11c）、白细胞（CD45）和单核细胞/巨噬细胞（CD68）的评估。使用数字图像分析，测量有/无小叶炎的小叶之间的免疫细胞密度并进行比较。评估了11个正常乳腺组织样本中的109个小叶；31个有小叶炎，78个没有。免疫细胞在所有正常样本中呈现一致的模式，主要定位于小叶而非基质。无论小叶炎状态如何，大多数小叶都显示有CD8 +、CD11c +、CD45 +和CD68 +细胞，而CD4 +和CD20 +细胞密度较低。CD11c +和CD8 +细胞始终与小叶上皮的基底部分紧密相关。在有小叶炎的小叶中观察到CD4 +、CD8 +、CD20 +和CD45 +细胞的密度显著更高。相比之下，单核细胞/巨噬细胞和树突状细胞的密度不随小叶炎而变化。在正常乳腺组织中，髓样细胞和淋巴细胞存在并定位于小叶，细胞毒性T细胞和树突状细胞直接与上皮整合。有小叶炎的小叶具有明显更多的适应性免疫（B和T）细胞，但树突状细胞或单核细胞/巨噬细胞没有增加。这些发现表明正常乳腺组织中存在活跃且动态的黏膜免疫系统。
