A research team at the Montefiore Einstein Comprehensive Cancer Center (MECCC) has discovered a natural immune response in mice that prevents disseminated cancer cells (DCCs) from forming tumors in other parts of the body. This finding, published today in the journal Cell, offers new insights into a critical challenge in cancer treatment: metastasis.

Metastatic disease, which occurs when cancer spreads from its original site to distant organs, is responsible for the majority of cancer-related deaths. While researchers have made progress in understanding how cancer cells escape their primary tumors, the reasons some metastases emerge only years later remain largely unexplained.

“Preventing or curing metastases is the most critical challenge in cancer,” said study leader Dr. Julio Aguirre-Ghiso. “Our findings could lead to innovative strategies for managing metastatic disease.”

In their studies involving three mouse models of metastatic breast cancer, Aguirre-Ghiso and his team found that when DCCs migrate to the lungs, they are kept in a dormant state by immune cells known as alveolar macrophages. These specialized macrophages, which serve as the lung’s first line of defense against pathogens and pollutants, play a crucial role in maintaining DCC dormancy by secreting a protein called TGF-b2, which inhibits cancer cell activation.

The researchers confirmed the importance of these macrophages by depleting them in mice, leading to a significant increase in activated DCCs and subsequent metastases in the lungs.

“As DCCs become more aggressive, they can evade the pro-dormancy signals from alveolar macrophages, allowing them to ‘wake up’ and initiate metastases,” Aguirre-Ghiso explained.

This research sheds light on how immune cells regulate DCCs and opens the door to potential new therapies for preventing metastasis. Aguirre-Ghiso noted that future strategies might involve enhancing macrophage signaling to keep DCCs dormant or preventing older DCCs from becoming resistant to dormancy signals.