The circulating immune cell landscape stratifies metastatic burden in breast cancer patients

Advanced breast cancers show varying degrees of metastasis; however, reliable biomarkers of metastatic disease progression remain unknown. In circulation, immune cells are the first line of defence against tumour cells. Herein, using >109,591 peripheral blood mononuclear cells from healthy individuals and breast cancer patients, we tested whether molecular traits of the circulating immune cells, probed with single-cell transcriptomics, can be used to segregate metastatic profiles. Our analyses revealed significant compositional and transcriptional differences in PBMCs of patients with restricted or high metastatic burden versus healthy subjects. The abundance of T cell and monocyte subtypes segregated cancer patients from healthy individuals, while memory and unconventional T cells were enriched in low metastatic burden disease. The cell communication axes were also found to be tightly associated with the extent of metastatic burden. Additionally, we identified a PBMC-derived metastatic gene signature capable of discerning metastatic condition from a healthy state. Our study provides unique molecular insights into the peripheral immune system operating in metastatic breast cancer, revealing potential new biomarkers of the extent of the metastatic state. Tracking such immune traits associated with metastatic spread could complement existing diagnostic tools.