title: In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium.
abstract: Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches.
authors.affiliation: Center for Information Services and High Performance Computing, Technische Universität Dresden, 01062 Dresden, Germany.|Braunschweig Integrated Centre of Systems Biology, Helmholtz Center for Infectious Research, 38124 Braunschweig, Germany.
authors.forename: J C L
authors.initials: JC
authors.lastname: Alfonso
authors.affiliation: Institute for Pathology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: N S
authors.initials: NS
authors.lastname: Schaadt
authors.affiliation: Definiens AG, 80636 Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schönmeyer
authors.affiliation: Definiens AG, 80636 Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Brieu
authors.affiliation: Engineering Science, Computer Science and Imaging Laboratory, Université de Strasbourg, 67400 Strasbourg, France.|Modelling, Intelligence, Process and Systems, Université de Haute Alsace, 68093 Mulhouse, France.
authors.forename: G
authors.initials: G
authors.lastname: Forestier
authors.affiliation: Engineering Science, Computer Science and Imaging Laboratory, Université de Strasbourg, 67400 Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Wemmert
authors.affiliation: Institute for Pathology, Hannover Medical School, 30625 Hannover, Germany.|Institute of Neuropathology, University Clinic Freiburg, 79117 Freiburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Feuerhake
authors.affiliation: Center for Information Services and High Performance Computing, Technische Universität Dresden, 01062 Dresden, Germany.|Braunschweig Integrated Centre of Systems Biology, Helmholtz Center for Infectious Research, 38124 Braunschweig, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hatzikirou