CD169+ lymph node macrophages have protective functions in mouse breast cancer metastasis

Cell Rep. 2021 Apr 13;35(2):108993. doi: 10.1016/j.celrep.2021.108993.


Although the contribution of macrophages to metastasis is widely studied in primary tumors, the involvement of macrophages in tumor-draining lymph nodes (LNs) in this process is less clear. We find CD169+ macrophages as the predominant macrophage subtype in naive LNs, which undergo proliferative expansion in response to tumor stimuli. CD169+ LN macrophage depletion, using an anti-CSF-1R antibody or clodronate-loaded liposomes, leads to increased metastatic burden in two mouse breast cancer models. The expansion of CD169+ macrophages is tightly connected to B cell expansion in tumor-draining LNs, and B cell depletion abrogates the effect of CD169+ macrophage absence on metastasis, indicating that the CD169+ macrophage anti-metastatic effects require B cell presence. These results reveal a protective role of CD169+ LN macrophages in breast cancer metastasis and raise caution for the use of drugs aiming at the depletion of tumor-associated macrophages, which might simultaneously deplete macrophages in tumor-draining LNs.

Keywords: CD169+ macrophages; breast cancer metastasis; distant organ metastasis; lymph node macrophages; tumor-associated macrophages; tumor-draining lymph node.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Biomarkers / metabolism
  • Cell Proliferation
  • Female
  • Gene Expression
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Macrophages / cytology
  • Macrophages / immunology*
  • Mammary Glands, Animal / immunology*
  • Mammary Glands, Animal / pathology
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / immunology
  • Monocytes / pathology
  • Sialic Acid Binding Ig-like Lectin 1 / genetics*
  • Sialic Acid Binding Ig-like Lectin 1 / immunology
  • Tumor Burden


  • Biomarkers
  • Sialic Acid Binding Ig-like Lectin 1
  • Siglec1 protein, mouse