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Stress Can Activate Neutrophils, a Type of Immune Cells, to Reawaken Dormant Tumor Cells and Trigger Cancer Recurrence 

Despite dramatic progress in cancer therapy, long-term survival is hindered when cancer returns. Tumor cells that escape initial treatment can travel to distant sites in the body and remain hidden there silently for years. They don’t actively multiply until they receive the right stimuli that coax them out of their sleep. When these “dormant” cells reawaken, they divide and give rise to new tumors often very difficult to treat. 
A new study by Wistar and collaborators at the University of Pittsburgh reveals that stress is one factor involved in reawakening dormant cells. Michela Perego, Ph.D., a research assistant professor in The Wistar Institute Cancer Center and first author of the paper published in the journal Science Translational Medicine, helps us understand the importance of these new findings.

Q: Dormant cells are quite elusive and the mechanisms underlying their reawakening are not well understood. How did you tackle them?

A: We decided to create a mouse model of tumor dormancy that would allow us to look at the process with a comprehensive, whole-body approach by tracking dormant cells over time and studying their interaction with the surrounding environment.

Q: What did you discover thanks to this model and confirmed in lung cancer patients?

A: We found that neutrophils, a type of immune cells, can be activated by stress hormones to produce some special lipids that are responsible for the reawakening dormant tumor cells. Accordingly, we observed that patients who experience early recurrence have higher levels of stress hormones and markers of neutrophils activation in their blood compared to patients that have late or no cancer recurrence.

Q: What do your results suggest about stress management in patients recovering from cancer? Does your study point to any potential strategies that might help reduce the risk of cancer recurrence?

A: Our data suggest that stress hormone levels should be monitored in patients recovering from cancer and that managing stress to keep those hormones at bay would be beneficial to prolong remission. Of course, multiple factors concur to determine recurrence. We have uncovered stress as one of the mechanisms involved and propose that adjuvant therapy to reduce stress hormone levels could be a valid addition to standard cancer treatment to prevent dormant cells reawakening and cancer relapse.

Publication information: “Reactivation of dormant tumor cells by modified lipids derived from stress-activated neutrophils”, Science Translational Medicine (2020)