Emerging functions of C/EBPß in breast cancer.

Breast tumorigenesis relies on complex interactions between tumor cells and their surrounding microenvironment, orchestrated by tightly regulated transcriptional networks. C/EBPß is a key transcription factor that regulates the proliferation and differentiation of multiple cell types and modulates a variety of biological processes such as tissue homeostasis and the immune response. In addition, C/EBPß has well-established roles in mammary gland development, is overexpressed in breast cancer, and has tumor-promoting functions. In this review, we discuss context-specific roles of C/EBPß during breast tumorigenesis, isoform-specific gene regulation, and regulation of the tumor immune response. We present challenges in C/EBPß biology and discuss the importance of C/EBPß isoform-specific gene regulation in devising new therapeutic strategies.

Diverse Macrophage Populations Contribute to the Inflammatory Microenvironment in Premalignant Lesions During Localized Invasion.

Myeloid cell heterogeneity remains poorly studied in breast cancer, and particularly in premalignancy. Here, we used single cell RNA sequencing to characterize macrophage diversity in mouse pre-invasive lesions as compared to lesions undergoing localized invasion. Several subpopulations of macrophages with transcriptionally distinct profiles were identified, two of which resembled macrophages in the steady state. While all subpopulations expressed tumor-promoting genes, many of the populations expressed pro-inflammatory genes, differing from reports in tumor-associated macrophages. Gene profiles of the myeloid cells were similar between early and late stages of premalignancy, although expansion of some subpopulations occurred. These results unravel macrophage heterogeneity in early progression and may provide insight into early intervention strategies that target macrophages.