Cell Reports (Apr 2021)

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

  • Carlotta Tacconi,
  • Catharina D. Commerford,
  • Lothar C. Dieterich,
  • Simon Schwager,
  • Yuliang He,
  • Kristian Ikenberg,
  • Ekaterina Friebel,
  • Burkhard Becher,
  • Sònia Tugues,
  • Michael Detmar

Journal volume & issue
Vol. 35, no. 2
p. 108993

Abstract

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Summary: 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.

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