During cancer metastasis, tumor cells invade distant tissues of the body to produce new tumors, making treatments less effective and drastically worsening the disease prognosis. However, new findings published in Nature Cell Biology have uncovered an intriguing cancer ecosystem, in which signals initiated by a primary tumor can lead to the freezing of secondary tumors. The work, carried out in mice and humans, comes from a team led by Garvan Institute of Medical Research and Harvard University.
"This new research has yielded that rare thing—a clue from the cancer itself about new possibilities to fight its spread,” said senior study co-author Christine Chaffer. “Our goal is to work out how we can mimic this 'freezing' of secondary cancers, so that one day we might influence all breast cancers to keep their secondary tumors in check."
From work in mice, the team found that primary breast tumors can promote additional cancer cells, called “metastasis-inducing cancer cells (MIC)” to break away and establish tumors in new areas of the body. The primary tumor, by provoking the immune system, is then able to send out immune response signals to the secondary breakaway tumors. Surprisingly, the response appears to freeze the growth of the breakaway MICs.
“We discovered that certain primary tumors elicit a systemic inflammatory response involving interleukin-1β (IL-1β)-expressing innate immune cells that infiltrate distant MIC microenvironments, the team reported in the paper. “At the metastatic site, IL-1β maintains MICs in a ZEB1-positive differentiation state, preventing MICs from generating highly proliferative E-cadherin-positive progeny.”
The team believes that before establishing a new tumor, breakaway MICs are in an intermediate and vulnerable state. At this point, intervention by the immune system can prove effective.
In a group of 215 breast cancer patients at high risk for developing metastasis, those with high levels of a similar type of immune response were found to have better overall survival rates. This indirect observation in a human population poses a promising application of the immune mechanism. The team hopes to further understand elements of the immune response for use in cancer treatments.
"We want to understand exactly what the tumor is releasing to activate this immune response, and how immune cells are targeting the secondary sites," explained Chaffer. "In principle, all of these steps present therapeutic opportunities that could be used to stop a cancer from developing any further."