Immune cells regulate breast development, function and cancer, but little is known about the mechanisms involved. Broadly, we know that duct growth and tumorigenesis are negatively regulated by T cells, while mast cells, eosinophils and macrophages promote morphogenesis and remodelling. Macrophages also reduce the effectiveness of cancer treatments and plasma cells provide protective IgA antibodies to breastfeeding infants. We want to determine how these functions are carried out and how breast tissue instructs these immune cells in their unique roles.
We previously used 3D imaging and intravital imaging to discover a unique population of ‘ductal’ macrophages that survey the entire mammary epithelium with fine dendrites. We have also revealed the location of plasma cells that arrive in the breast during lactation. We are now implementing spatial transcriptomics to reveal how neighbouring cells communicate and influence immune cell function. We are also developing methods for gene editing of the mammary epithelium and stromal cells to determine the role of individual niche signals. Finally, novel mouse models for targeted breast immune cell ablation are helping us to define breast immune cell function more accurately. Through these efforts, we hope to discover new avenues for immunotherapeutic treatment of breast diseases like inflammation and cancer.