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

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.