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The role of the systemic immune environment in promoting metastasis remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study describes peripheral blood immune alterations associated with LN metastasis in BC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Peripheral blood mononuclear cells (PBMCs) from six BC patients with LN metastasis\u2010positive (Pos) and negative (Neg) underwent single\u2010cell RNA\/T\u2010cell receptor sequencing (scRNA\u2010seq\/scTCR\u2010seq). Findings were validated by in vitro\u00a0functional experiments and single\u2010cell data from additional 14 BC tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>scRNA\u2010seq identified pro\u2010metastatic immune subpopulations enriched in Pos group: neutrophil_RSAD2 with expressing interferon\u2010stimulated genes (ISG) and neutrophil_MMP9 with expressing pro\u2010angiogenic factors, and immunosuppressive CD4Treg_FOXP3 and cytotoxic\u2010exhausted TandNK cells CD8Teff_GZMH and NKT_GNLY; and anti\u2010metastatic CD8Teff_CCL5 in Neg group. Pos group showed expanded large clonal T cells expressing cytotoxicity markers GZMH\/GNLY. LGALS9\u2012HAVCR2 checkpoint interactions were elevated in Pos group through the neutrophil\/mononuclear phagocyte (MP)\u2012MP\/TandNK axis, which was associated with an immunosuppressive microenvironment and metastatic status. These pro\u2010 and anti\u2010metastatic immune signatures and LGALS9\u2012HAVCR2 axis were confirmed by in vitro experiments and consistently observed in BC tissues. Furthermore, functional co\u2010culture assays established a causal relationship: interferon\u2010stimulated neutrophils secreted LGALS9 and impaired their cytotoxic function on T cells. Conversely, neutralising LGALS9 or disrupting this axis restored T\u2010cell\u2010mediated tumour cell killing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LN metastasis is associated with a remodelled systemic immunity, enriches immunosuppressive neutrophils and TandNK cells and activates LGALS9\u2012HAVCR2 signalling. These findings reveal immune signatures associated with LN metastasis status and identify candidate biomarkers and therapeutic targets warranting further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70686","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:36:51Z","timestamp":1780990611000},"source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010cell profiling reveals peripheral blood immune landscape remodelling in breast cancer lymph node metastasis"],"prefix":"10.1002","volume":"16","author":[{"given":"Bo","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Breast Cancer Cancer Center Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University  Guangzhou China"},{"name":"School of Medicine South China University of Technology  Guangzhou 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