Institute of Pathology, Neuropathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
Breast Cancer Res Treat. 2017 Jul;164(2):305-315. doi: 10.1007/s10549-017-4239-z. Epub 2017 Apr 25.
To improve microscopic evaluation of immune cells relevant in breast cancer oncoimmunology, we aim at distinguishing normal infiltration patterns from lymphocytic lobulitis by advanced image analysis. We consider potential immune cell variations due to the menstrual cycle and oral contraceptives in non-neoplastic mammary gland tissue.
Lymphocyte and macrophage distributions were analyzed in the anatomical context of the resting mammary gland in immunohistochemically stained digital whole slide images obtained from 53 reduction mammoplasty specimens. Our image analysis workflow included automated regions of interest detection, immune cell recognition, and co-registration of regions of interest.
In normal lobular epithelium, seven CD8[Formula: see text] lymphocytes per 100 epithelial cells were present on average and about 70% of this T-lymphocyte population was lined up along the basal cell layer in close proximity to the epithelium. The density of CD8[Formula: see text] T-cell was 1.6 fold higher in the luteal than in the follicular phase in spontaneous menstrual cycles and 1.4 fold increased under the influence of oral contraceptives, and not co-localized with epithelial proliferation. CD4[Formula: see text] T-cells were infrequent. Abundant CD163[Formula: see text] macrophages were widely spread, including the interstitial compartment, with minor variation during the menstrual cycle.
Spatial patterns of different immune cell subtypes determine the range of normal, as opposed to inflammatory conditions of the breast tissue microenvironment. Advanced image analysis enables quantification of hormonal effects, refines lymphocytic lobulitis, and shows potential for comprehensive biopsy evaluation in oncoimmunology.
为了提高乳腺癌肿瘤免疫学中与免疫细胞相关的微观评估水平，我们旨在通过先进的图像分析，将正常浸润模式与淋巴细胞性小叶炎区分开来。我们考虑了非肿瘤性乳腺组织中因月经周期和口服避孕药而导致潜在的免疫细胞变化。
在从 53 例乳房缩小整形术标本中获得的免疫组织化学染色数字全切片图像的解剖学背景下，分析了淋巴细胞和巨噬细胞的分布。我们的图像分析工作流程包括自动感兴趣区域检测、免疫细胞识别以及感兴趣区域的配准。
在正常小叶上皮中，平均每 100 个上皮细胞存在 7 个 CD8[Formula: see text]淋巴细胞，其中约 70%的 T 淋巴细胞沿基底细胞层排列，与上皮细胞紧密相邻。在自发月经周期中，黄体期 CD8[Formula: see text]T 细胞的密度比卵泡期高 1.6 倍，在口服避孕药的影响下增加了 1.4 倍，且与上皮细胞增殖无关。CD4[Formula: see text]T 细胞很少见。丰富的 CD163[Formula: see text]巨噬细胞广泛分布，包括间质间隙，在月经周期中变化不大。
不同免疫细胞亚型的空间模式决定了乳腺组织微环境的正常范围，而不是炎症状态。先进的图像分析能够定量评估激素的影响，细化淋巴细胞性小叶炎，并为肿瘤免疫学中的全面活检评估提供潜力。
