Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals the reduction of CD169⁺ macrophages by metastatic breast cancers

Abstract

Background: Breast cancer cells suppress the host immune system to efficiently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we aimed to comprehensively characterise the effects of breast cancers on immune cells in the lymph nodes.Methods: We collected non-metastatic and metastatic lymph node samples from 6 patients with breast cancer with lymph node metastasis. We performed bulk transcriptomics, spatial transcriptomics, and imaging mass cytometry to analyse the obtained lymph nodes. Furthermore, we conducted histological analyses against a larger patient cohort (474 slices from 58 patients).Findings: The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169+ lymph node sinus macrophages, an initiator of anti-cancer immunity, was reduced in metastatic lymph nodes (36.7 ± 21.1 vs 7.3 ± 7.0 cells/mm², p = 0.0087), whereas the numbers of other major immune cell types were unaltered. We also detected that the infiltration of CD169⁺ macrophages into metastasised cancer tissues differed by section location within tumours, suggesting that CD169⁺ macrophages were gradually decreased after anti-cancer reactions. Furthermore, CD169+ macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging (p = 0.022). Interpretation: We concluded that lymph nodes with breast cancer metastases have fewer CD169⁺ macrophages, which may be detrimental to the activity of anti-cancer immunity.