Single cell profiling of primary and paired metastatic lymph node tumors in breast cancer patients

Lymph node metastasized tumours (LNMT) in breast cancer have not been comprehensively characterised. Here, the authors perform single cell RNA sequencing analysis of paired primary and LNMT breast cancer samples and suggest a more immunosuppressive tumour microenvironment in the latter. The microenvironment of lymph node metastasized tumors (LNMT) determines tumor progression and response to therapy, but a systematic study of LNMT is lacking. Here, we generate single-cell maps of primary tumors (PTs) and paired LNMTs in 8 breast cancer patients. We demonstrate that the activation, cytotoxicity, and proliferation of T cells are suppressed in LNMT compared with PT. CD4(+)CXCL13(+) T cells in LNMT are more likely to differentiate into an exhausted state. Interestingly, LAMP3(+) dendritic cells in LNMT display lower T cell priming and activating ability than in PT. Additionally, we identify a subtype of PLA2G2A(+) cancer-associated fibroblasts enriched in HER2(+) breast cancer patients that promotes immune infiltration. We also show that the antigen-presentation pathway is downregulated in malignant cells of the metastatic lymph node. Altogether, we characterize the microenvironment of LNMT and PT, which may shed light on the individualized therapeutic strategies for breast cancer patients with lymph node metastasis.

Automated summary

This study characterizes the microenvironment of lymph node metastasized tumors (LNMT) and primary tumors (PT) in breast cancer. The results show that T cell activation, cytotoxicity, and proliferation are suppressed in LNMT compared to PT. CD4(+)CXCL13(+) T cells in LNMT are more likely to become exhausted. LAMP3(+) dendritic cells in LNMT have lower T cell priming and activating ability compared to PT. PLA2G2A(+) cancer-associated fibroblasts, enriched in HER2(+) breast cancer patients, promote immune infiltration. Additionally, the antigen-presentation pathway is downregulated in malignant cells of the metastatic lymph node.