In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium

Authored by J C L Alfonso, N S Schaadt, R Schoenmeyer, N Brieu, G Forestier, C Wemmert, F Feuerhake, H Hatzikirou

Date Published: 2016

DOI: 10.1038/srep33322

Sponsors: German Federal Ministry of Education and Research (BMBF) Center for Information Services and High Performance Computing (ZIH)

Platforms: No platforms listed

Model Documentation: Other Narrative Flow charts Mathematical description

Model Code URLs: Model code not found

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.

Tags

inflammation cancer T-cells Dna-damage Resting human-breast Menstrual-cycle Mammary-gland Tumor immunogenicity Apoptotic cells Transgenic mice