Daniela F. Quail1,2, Morag Park1,3, Alana L. Welm4 and H. Atakan Ekiz5 1Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec H3A 1A3, Canada 2Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada 3Departments of Biochemistry, Oncology, McGill University, Montreal, Quebec H3G 1Y6, Canada 4Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA 5Department of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce, 35430 Urla, Izmir, Turkey Correspondence: atakanekiziyte.edu.tr

Our ability to interrogate the tumor immune microenvironment (TIME) at an ever-increasing granularity has uncovered critical determinants of disease progression. Not only do we now have a better understanding of the immune response in breast cancer, but it is becoming possible to leverage key mechanisms to effectively combat this disease. Almost every component of the immune system plays a role in enabling or inhibiting breast tumor growth. Building on early seminal work showing the involvement of T cells and macrophages in controlling breast cancer progression and metastasis, single-cell genomics and spatial proteomics approaches have recently expanded our view of the TIME. In this article, we provide a detailed description of the immune response against breast cancer and examine its heterogeneity in disease subtypes. We discuss preclinical models that enable dissecting the mechanisms responsible for tumor clearance or immune evasion and draw parallels and distinctions between human disease and murine counterparts. Last, as the cancer immunology field is moving toward the analysis of the TIME at the cellular and spatial levels, we highlight key studies that revealed previously unappreciated complexity in breast cancer using these technologies. Taken together, this article summarizes what is known in breast cancer immunology through the lens of translational research and identifies future directions to improve clinical outcomes.