Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland; Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
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.
尽管巨噬细胞在原发性肿瘤中的转移作用已得到广泛研究，但它们在肿瘤引流淋巴结（LNs）中的作用尚不清楚。我们发现 CD169 巨噬细胞是未成熟 LNs 中的主要巨噬细胞亚型，它们会对肿瘤刺激发生增殖扩张。使用抗 CSF-1R 抗体或载有氯膦酸盐的脂质体耗竭 CD169 LN 巨噬细胞，会导致两种小鼠乳腺癌模型中的转移负担增加。CD169 巨噬细胞的扩张与肿瘤引流 LNs 中 B 细胞的扩张紧密相关，而 B 细胞耗竭则消除了 CD169 巨噬细胞缺失对转移的影响，表明 CD169 巨噬细胞的抗转移作用需要 B 细胞的存在。这些结果揭示了 CD169 LN 巨噬细胞在乳腺癌转移中的保护作用，并提醒人们在使用旨在耗竭肿瘤相关巨噬细胞的药物时要谨慎，因为这些药物可能会同时耗竭肿瘤引流 LNs 中的巨噬细胞。
