findings by SWCRF grantees at Mount Sinai reveal how immune cells factor in early breast cancer spread and may produce new therapies for early-on cancer metastasis

 

Julio Aguirre-Ghiso, PhD

Donor support for the Samuel Waxman Cancer Research Foundation has helped discover a crucial role played by immune cells in the formation of early-stage breast cancer metastasis. Findings from research at the Icahn School of Medicine at Mount Sinai funded in part by the SWCRF showed that normal immune cells called macrophages, which are part of healthy breast tissue residing in tissue surrounding milk ducts, play a major role in early breast cancer cells leaving the breast to spread to other parts of the body, potentially creating metastasis before a tumor has even developed.  These findings were published in the science journal  Nature Communications.

Scientific Approach

The macrophages play a role in mammary gland development by regulating how milk ducts branch out through breast tissue. Many studies have also proven the importance of macrophages in metastasis development but in models of advanced large tumors and metastasis. However, by studying human samples, mouse tissues and using breast organoids, which are miniaturized and simplified versions of breast tissue produced in the lab, this research found that in very early cancer lesions, macrophages are attracted to enter the breast ducts where they act to trigger a chain reaction that brings early cancer cells out of the breast, said lead researcher Dr. Julio Aguirre-Ghiso, PhD, Professor of Oncological Sciences, Otolaryngology, Medicine, Hematology and Medical Oncology at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

This research shows that macrophages’ relationship with normal breast cells is co-opted by early cancer cells that activate the HER2 oncogene and aids in this newly-discovered role of these immune cells promoting early cancer dissemination. This work provides proof that macrophages drive early cancer cell dissemination and impressively affecting late-stage metastatic disease.

Clinical Implications

The findings from this study could eventually help pinpoint biomarkers to identify cancer patients that may be at risk of carrying sleeping metastatic cells due to these macrophages and potentially lead to the development of novel therapies that prevent early on cancer metastasis.

This study, and future investigation, of the microenvironment surrounding tumor and immune cells in early breast cancer patients can help to identify those patients who are at high risk of developing metastasis, potentially requiring closer monitoring. Early treatment of high-risk patients may prevent the formation of deadly metastasis better than current standard of treating metastatic disease only once it has occurred, said key researcher Miriam Merad, MD, PhD, Director of the Precision Immunology Institute and the Human Immune Monitoring Center and co-leader of the Cancer Immunology program at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

“In this study and in our previous studies, we present mechanisms governing early dissemination," Dr. Aguirre-Ghiso said. "This work further sheds light onto the mysterious process of early dissemination and cancer of an unknown primary tumor.”

Researchers hope to build on this study by identifying which macrophages specifically control early dissemination. They also hope to further detail how early disseminated cancer cells interact with macrophages in the lungs where metastases eventually form and how this interaction can be targeted to prevent metastasis. 

 

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