Appreciation of the relationships among heterogeneous ER+ cancer cells and associated stromal cells, including not only macrophages of various polarization states, but also other cells of the myeloid lineage, CD8+ and Treg lymphocytes, CAFs and vascular endothelium, is critical to understanding ER+ disease, and how these relationships evolve with tumor progression, disease site, and therapies. The gene discussed is CD8A; the disease is neoplasm.