Immune Cells that Prevent Metastatic Cancer Cells from Proliferating After Migration
If there were a reliable way to prevent metastasis, the spread of cancerous cells throughout the body and generation of secondary tumors, few types of cancer would be life-threatening in the context of today's medical capabilities. Thus there is a lot to be said for the various lines of research aimed at finding ways to sabotage metastasis. Here researchers attempt to answer the question of why migrated metastatic cells sometimes fail to establish a secondary tumor, and point to a population of immune cells that may prove to be a useful target for anti-metatasis immunotherapy.
Cells that migrate from primary tumors and seed metastatic tumors are called disseminated cancer cells (DCCs). Some DCCs behave aggressively, immediately starting tumors in new tissue, while others remain in a state of suspended animation referred to as dormancy. "It's long been a mystery how some DCCs can remain in tissues for decades and never cause metastases, and we believe we've found the explanation." Breast cancer and many other types of cancer metastasize to the lungs. In research involving three mouse models of metastatic breast cancer, researchers determined that when breast cancer DCCs spread to the lung's alveoli, they are kept in a dormant state by immune cells known as alveolar macrophages.
Confirming the importance of alveolar macrophages in keeping DCCs dormant, researchers found that depleting them in the mice significantly increased the number of activated DCCs and subsequent metastases in their lungs compared to mice with normal levels of the immune cells. As DCCs become more aggressive, the researchers found, they become resistant to the pro-dormancy signals produced by alveolar macrophages. Ultimately, this evasion mechanism enables some DCCs to "wake up" from dormancy and reactivate to form metastases. Understanding how immune cells keep DCCs in check could lead to new anti-metastatic cell therapies among other strategies. For example, it may be possible to strengthen macrophage signaling so that DCCs never awaken from dormancy or find ways to prevent older DCCs from becoming resistant to dormancy signaling.