Several single-cell studies have reported transcriptomic, genomic and epigenomic dysregulation in breast cancer tissue. However, the peripheral immune landscape of breast cancer patients remains poorly understood. We report the analysis of the single-cell transcriptomes of more than 110,000 peripheral blood mononuclear cells (PBMCs) of healthy and metastatic breast cancer patients. Integrated analysis revealed depleted memory B cells and T cell subpopulations, including transitional CD8 T, CD4 naïve, CD4 ribosome and MAIT cells in the circulating immune landscape of metastatic breast cancer patients. Nevertheless, metastatic breast cancer patients showed marked enrichment of pro-inflammatory NKG7 high monocytes, M1 macrophages, migratory myeloid, T memory stem cells, and CD4 T effector memory and CD4 T central memory cells.
Interrogation of single-cell transcriptomes based on metastatic disease state revealed distinct compositional and transcriptional changes in PBMCs correlated with the metastatic burden. The cell communication axes, such as cell-cell contact, ECM-receptor interactions, and cytokine transcription profiles, were tightly associated with the metastatic burden. Our study provides unique molecular insight into the peripheral immune system operating in metastatic breast cancers and identified novel surrogate biomarkers of metastatic disease.