Australian researchers from Walter and Eliza Hall Institute have discovered a new form of immune cells within the ducts of the breast that keeps the breasts healthy. The study was published this week in the journal Nature Cell Biology.

The researchers explain that they found immune cells called macrophages. The term macrophage from Ancient Greek means "big" (macro) and (phage) "eaters." These macrophages are essential for the normal formation and functioning of the mammary glands, they wrote. The immune cells regulate one of the vital processes of the mammary ducts. The team explains that mammary ducts of breast ducts are thin tubules where milk is produced and then is transported to the nipples for lactation. These ducts are also one of the major sites where cancers appear.

Macrophages are important cells of the immune system that are formed in response to an infection or accumulating damaged or dead cells. Macrophages are large, specialized cells that recognize, engulf, and destroy target cells.

Image Credit: Alpha Tauri 3D Graphics/Shutterstock.com

To find out the immune cell machinery within the breasts, the team of researchers used three-dimensional (3D) imaging techniques in real-time. The team looked at the movement of the immune cells when infective organisms threaten the ducts. These immune cells, they saw, were "gobbling up" the dead and dying cells that originally produce milk. Once lactation or breast milk production stops, these milk-producing cells need to be cleared up, say the researchers. The researchers believe that if more insights could be obtained about these cells, it could help breast cancer research.

The preclinical study was led by researchers Dr. Caleb Dawson, Professor Geoff Lindeman, and Professor Jane Visvader, along with Dr. Anne Rios.

Researchers explain that breast ducts have milk-producing cells that produce milk during lactation. Throughout the life of a woman, these cells and the whole of the breast undergoes several changes during puberty, pregnancy, lactation and after menopause. The ducts branch out and develop when milk needs to be produced during lactation. After lactation is over, these cells need to stop. Researchers believe that while the milk-producing cells are essential, these duct cells are often the sites of origin of breast cancers.

The mammary gland is a dynamic organ that undergoes dramatic remodeling throughout life. The branching ducts bloom to form milk-producing 'factories' in lactation, which must be eliminated once lactation stops as part of a process called involution. Image Credit: Dr Caleb Dawson, Walter and Eliza Hall Institute

Dr. Dawson explained that they were looking at these important cells using high-resolution imaging techniques and found these immune cells that play a role in maintaining the health of the breast tissues. He said, "We discovered an entirely new population of specialized immune cells, which we named ductal macrophages, squeezed in between two layers of the mammary duct wall." He added, "We were excited to find that these cells play an essential role at a pivotal point in mammary gland function called involution when lactation stops, milk-producing cells die, and breast tissue needs to remodel back to its original state. We watched incredulously as the star-shaped ductal macrophages probed with their arms and ate away at dying cells. The clearing action performed by ductal macrophages helps redundant milk-producing structures to collapse, allowing them to return to a resting state successfully."

As a next step, they removed these newly found ductal macrophages from the mammary ducts and found that other mammary immune cells could not carry out these essential processes within the breasts and the ducts.

Professor Visvader explained that understanding these mammary duct-specific macrophages was a step towards explaining the interactions between ductal cells and the immune system and would also explain the development of the mammary glands. She said, "As breast cancer researchers, there is a need to understand which cells are doing what, so that we can identify how these intricate cellular processes become dysregulated, such as in the case of breast cancers."

Dr. Dawson and his team believe that this finding could help understand not only breast development but also how the breasts change during puberty, pregnancy, lactation, and breast cancer. He said, "We also want to investigate the role that these duct-specific immune cells play in helping cancer to grow and spread. Ductal macrophages are spread throughout the mammary ducts. As cancer grows, these macrophages also increase in number. We suspect that there's the potential for ductal macrophages to inadvertently dampen the body's immune response, which would have dangerous implications for the growth and spread of cancer in these already prone sites."

Professor Visvader also explained that they aimed to understand the functions of these cells. She said, "Given that tumor macrophages likely promote the growth of the tumor, blocking their activity could serve as a treatment strategy for breast cancer."

This study was funded by the National Health and Medical Research Council, the National Breast Cancer Foundation, the Australian Cancer Research Foundation, The Qualtrough Cancer Research Fund, Cure Cancer Australia, and the Victorian Government.

Journal reference:

Dawson, C.A., Pal, B., Vaillant, F. et al. Tissue-resident ductal macrophages survey the mammary epithelium and facilitate tissue remodelling. Nat Cell Biol (2020). https://doi.org/10.1038/s41556-020-0505-0, https://www.nature.com/articles/s41556-020-0505-0

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