Abstract
Simple SummaryBreast cancer is a major health concern as it remains the deadliest for women worldwide. As for other cancer types, the immune system is determinant for how the body fights the tumor and responds to therapy. Better medical care and therapy assignment can thus be obtained by a deeper understanding of the immune state of breast cancer patients and how it changes with disease and treatment. Such information becomes more relevant and accessible if collected easily from a blood test. This review summarizes current knowledge on breast cancer patients’ immune profile obtained from peripheral blood and serves as a starting point for further investigation. Finally, we discuss the latest advances and current challenges in experimental models to study the interactions between human cancer and immune cells, with the intent of bridging the gap between patient immune profiling and functional and therapeutic significance.Breast cancer is the deadliest female malignancy worldwide and, while much is known about phenotype and function of infiltrating immune cells, the same attention has not been paid to the peripheral immune compartment of breast cancer patients. To obtain faster, cheaper, and more precise monitoring of patients’ status, it is crucial to define and analyze circulating immune profiles. This review compiles and summarizes the disperse knowledge on the peripheral immune profile of breast cancer patients, how it departs from healthy individuals and how it changes with disease progression. We propose this data to be used as a starting point for validation of clinically relevant biomarkers of disease progression and therapy response, which warrants more thorough investigation in patient cohorts of specific breast cancer subtypes. Relevant clinical findings may also be explored experimentally using advanced 3D cellular models of human cancer–immune system interactions, which are under intensive development. We review the latest findings and discuss the strengths and limitations of such models, as well as the future perspectives. Together, the scientific advancement of peripheral biomarker discovery and cancer–immune crosstalk in breast cancer will be instrumental to uncover molecular mechanisms and putative biomarkers and drug targets in an all-human setting.
Highlights
Breast cancer remains the leading cause of cancer-related deaths for women worldwide
For triple negative breast cancer (TNBC), Foulds et al found a specific inflammation-related mRNA signature, consisting of high expression of CD163 and CXCR4 and low expression of THBS1, which correlated with improved relapse-free survival in a cohort of 186 patients [64]
We have summarized the available knowledge of the peripheral immune landscape of breast cancer but, as it became clear, this is a field that still requires attentive interrogation and standardization to generate meaningful clinical information
Summary
Breast cancer remains the leading cause of cancer-related deaths for women worldwide. Concurrent with the evidence that immunotherapies are beneficial in breast cancer treatment, years of studies with thousands of patients have consistently showed that for early stage HER2+ and TNBC cases the presence and increased numbers of TIL are associated with better disease prognosis and response to therapy [24]. For this reason, it has been proposed to incorporate TIL analysis as predictive and prognostic biomarkers in clinical practice. We discuss the existing cellular models applicable to explore the mechanisms behind these relationships of peripheral immune state and disease progression, their strengths, and future developments
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