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

Abstract

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.