Nadine S Schaadt1, Juan Carlos López Alfonso2, Ralf Schönmeyer3, Anne Grote1, Germain Forestier4, Cédric Wemmert5, Nicole Krönke1, Mechthild Stoeckelhuber6, Hans H Kreipe1, Haralampos Hatzikirou2, Friedrich Feuerhake7,8. 1. Institute of Pathology, Neuropathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany. 2. Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany. 3. Definiens AG, Bernhard-Wicki-Straße 5, 80636, Munich, Germany. 4. MIPS, University of Haute Alsace, 12 rue des Freres Lumiere, 68093, Mulhouse, France. 5. ICube, University of Strasbourg, 300 bvd Sebastien Brant, 67412, Illkirch, France. 6. Department of Oral and Maxillofacial Surgery, Technische Universität München, Ismaningerstraße 22, 81675, Munich, Germany. 7. Institute of Pathology, Neuropathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany. Feuerhake.Friedrich@mh-hannover.de. 8. University Clinic of Freiburg, Institute for Neuropathology, Breisacher Str. 64, 76106, Freiburg, Germany. Feuerhake.Friedrich@mh-hannover.de.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Thomas E Rohan; Rhonda Arthur; Yihong Wang; Sheila Weinmann; Mindy Ginsberg; Sherene Loi; Roberto Salgado Journal: Breast Cancer Res Date: 2021-01-30 Impact factor: 6.466