Macrophage blockade in early breast cancer can reduce metastasis throughout life

Immune cells play a major role in early breast cancer even before a tumor is detectable. Disruption of macrophages and early cancer cells interaction can prevent early dissemination and consequently, metastasis in breast cancer patients.

HFSP Long-Term Fellow Maria Casanova-Acebes and colleagues
authored on Tue, 30 January 2018

Macrophages are immune cells that scavenge cell debris in homeostasis. In healthy breasts, these phagocytes play a major role during mammary duct development, regulating milk duct branching throughout breast tissue. Previous studies have provided insight into the role of macrophages in established large tumors, however their role during early tumor formation has remained unexplored.

Figure: Model of macrophage early dissemination.

In our study we have uncovered a role for tissue-resident macrophages in the mammary gland as instigating early cancer cells to leave the breast and invade other parts of the body. This escape from the growing tumor is the origin of new metastatic nodules, even before we are able to notice that a tumor is developing.

Taking advantage of human breast samples, murine models and breast organoids, we were able to establish that macrophages are attracted locally to breast ducts where they physically interact with cancer cells, which in turn triggers a cascade of events leading to the release of tumor cells into circulation. These circulating cancer cells will home in to the lung where a new tumor will develop. 

Our findings could eventually lead to identifying patients carrying these early disseminated cancer cells and targeting this unique population of macrophages in early phases of breast cancer, with the aim of developing new immunotherapies to avoid cancer metastasis.

Reference

Macrophages orchestrate breast cancer early dissemination and metastasis. Linde, N., Casanova-Acebes, M., Sosa, M.S., Mortha, A., Rahman, A., Farias, E., Harper, K., Tardio, E., Reyes Torres, I., Jones, J., et al. (2018). Nat Commun 9, 21. DOI: 10.1038/s41467-017-02481-5

PubMed link