Characterizing Immune and Epithelial Biomarkers in Triple-Negative Breast Cancer (TNBC) Progression Using the KBP Mouse Model.

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive subtype of breast cancer with limited therapies currently available due to the lack of targeted receptors. Macrophages and epithelial tumor cells, which are key cells present in the tumor microenvironment, have been acknowledged to play a significant role in disease progression and metastasis. The study aims to identify the tumor-immune biomarkers that contribute to cancer aggressiveness in a well-established K14cre; BRCA1^f/f; p53^f/f (KBP) TNBC mouse model that resembles aggressive human TNBC. Histological analysis showed abnormal cellular morphology, and CK14 immunohistochemical and immunofluorescence staining confirmed the basal-like epithelial characteristics across primary, early, and late metastatic sites, whereas CD68 immunohistochemical and immunofluorescence staining demonstrated macrophage infiltration with focal infiltration in early metastasis and widespread macrophage infiltration in late metastasis. Gene expression studies displayed differential expression of the following cytokines: CCL2 and CXCL5, which are involved in macrophage and neutrophil recruitment. Nonetheless, the project’s results illustrate the dynamic role of the immune microenvironment in the progression of TNBC and propose opportunities for developing therapeutics.