Neuromedin U drives immune suppression in aggressive prostate cancer
· News-MedicalDario C. Altieri, M.D., president & CEO, director of the Ellen and Ronald Caplan Cancer Center and Robert and Penny Fox Distinguished Professor at The Wistar Institute, and senior author on the studyWe already know that the immune system and cancers communicate with each other, which has led to transformative therapies for cancers that had once been thought of as untreatable. This study reveals that cancer is also communicating with the nervous system, potentially opening the door to new therapies for cancers that currently lack effective therapeutic options."
In a murine model, researchers looked at activity in tissue cells before cancer developed and found an excessive amount of NMU. This neurotransmitter usually does not play a pathological role in the human body, and is a key part of critical functions like regulating blood pressure, stress response and keeping hormones in check. But in NEPC, an overabundance of NMUs effectively block T cell migration to the prostate by activating neutrophils that suppress T cells: NMU-activated neutrophils work for the cancer before the cancer really forms by suppressing T cells that would normally lead the charge to mount an immune response.
Disrupting this pathway to stop the overproduction of NMU in NEPC could open new avenues for treatment, she added. "They could turn cold tumors hot, and when used together, make these tumors new targets for immunotherapy and present a new way to approach cancer that has proven nearly impossible to stop or slow down."
"Neuromedin U turned out to be a lynchpin," said Altieri. "The tumor uses it to build a shield of protective immune cells around it, and when the signal is removed, the shield comes down. For a cancer with limited options, identifying a target that reopens the door to immunotherapy is something we want to better understand."
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