biostudies-literatureEichin DAcademy of Finland (Suomen Akatemia)Syöpäsäätiö (Cancer Foundation Finland)10056https://www.ebi.ac.uk/biostudies/studies/S-EPMC12623973biostudies-literatureUnknown16(1)Cancer metastasis to sentinel lymph nodes (LNs) is often the first marker of potential disease progression. Although it is recognized that tumor-induced lymphangiogenesis facilitates metastasis into LNs in murine models, tumor-induced alterations in human lymphatic vessels remain obscure. Here we use single-cell RNA sequencing and high-resolution spatial transcriptomics to profile lymphatic endothelial cell (LEC) subsets in paired metastatic and non-metastatic LNs obtained from female patients with treatment-naïve breast cancer. Tumor metastasis decreases immunoregulatory LEC subsets, such as PD-L1⁺ subcapsular sinus LECs, while inducing an increase in capillary-like CD200⁺ HEY1⁺ LECs. Matrix Gla protein (MGP) is the most upregulated gene in metastatic LN LNature communicationsBreast cancer remodels lymphatics in sentinel lymph nodes.PMC12623973336269A2649A2473Hollmen MLehotina DLonnberg TEichin DPiipponen MAittokallio TUenaka MLeppanen MElima KBostrom PTakeda AKauko AKoskivuo IJalkanen SfalseBreast cancer remodels lymphatics in sentinel lymph nodes.Cancer metastasis to sentinel lymph nodes (LNs) is often the first marker of potential disease progression. Although it is recognized that tumor-induced lymphangiogenesis facilitates metastasis into LNs in murine models, tumor-induced alterations in human lymphatic vessels remain obscure. Here we use single-cell RNA sequencing and high-resolution spatial transcriptomics to profile lymphatic endothelial cell (LEC) subsets in paired metastatic and non-metastatic LNs obtained from female patients with treatment-naïve breast cancer. Tumor metastasis decreases immunoregulatory LEC subsets, such as PD-L1⁺ subcapsular sinus LECs, while inducing an increase in capillary-like CD200⁺ HEY1⁺ LECs. Matrix Gla protein (MGP) is the most upregulated gene in metastatic LN L2025-01-01T00:00:00Z2025 Nov2026-06-05T16:36:01.922Z2026-05-18T03:13:17.698ZS-EPMC126239734124912410.1038/s41467-025-64981-z