CD169+ lymph node macrophages have protective functions in mouse breast cancer metastasis
Carlotta Tacconi1, Catharina D Commerford1, Lothar C Dieterich1
1Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
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.
Insights
CD169-positive macrophages in lymph nodes protect against breast cancer metastasis. Their depletion, along with B cells, increases tumor spread, highlighting a crucial role in immune defense.
Area of Science:
- Immunology
- Oncology
- Cancer Metastasis
Background:
- Macrophages are key players in primary tumors, but their role in lymph node metastasis is less understood.
- Tumor-draining lymph nodes (LNs) are critical sites for cancer spread, yet the specific macrophage subtypes involved remain unclear.
Purpose of the Study:
- To investigate the role of macrophages within tumor-draining lymph nodes (LNs) in breast cancer metastasis.
- To identify specific macrophage subtypes in LNs and their contribution to anti-metastatic immunity.
Main Methods:
- Utilized mouse models of breast cancer.
- Depleted CD169-positive (CD169+) macrophages using anti-CSF-1R antibodies and clodronate-loaded liposomes.
- Investigated the interplay between CD169+ macrophages and B cells in the context of metastasis.
Main Results:
- CD169+ macrophages are the dominant subtype in naive LNs and expand upon tumor presence.
- Depletion of CD169+ macrophages significantly increased metastatic burden in breast cancer models.
- The anti-metastatic effect of CD169+ macrophages is dependent on the presence of B cells.
Conclusions:
- CD169+ macrophages in tumor-draining LNs exert a protective, anti-metastatic effect in breast cancer.
- Therapeutic strategies targeting tumor-associated macrophages require careful consideration to avoid depleting protective LN macrophages.
- The anti-metastatic function of CD169+ macrophages involves collaboration with B cells within the lymph node microenvironment.
