Study Reveals How Aggressive Prostate Cancer Blocks Immune Cells From The Start

Prostate cancer is often a manageable condition for many men. The American Cancer Society notes a five-year survival rate of 98 percent for the disease. However, there is a specific and aggressive form of the diagnosis that defies standard treatments. This variant is known as neuroendocrine prostate cancer, or NEPC. It is considered an "immunologically cold" tumor. This means it does not respond to the immunotherapy drugs that have revolutionized other forms of cancer care. Doctors often struggle with this specific type because it lacks T cells. T cells are critical components of our immune system that target and destroy cancer cells. Without them, standard immunotherapy cannot work. A new study from The Wistar Institute has identified a potential reason why this immune response fails. The researchers found a link between the nervous system and the rapid development of NEPC.

The study published in the journal Oncogene uncovered the work of a specific neurotransmitter. Researchers identified neuromedin U, or NMU, as a key player in this process. They found high levels of NMU in prostate cells during the very earliest phase of NEPC formation. This neurotransmitter usually supports critical functions in the human body. It helps regulate blood pressure, responds to stress, and keeps hormones in check. In the context of this cancer, however, the levels become excessive. This abundance of NMU effectively blocks the migration of T cells to the prostate. It does this by activating neutrophils. These neutrophils then suppress the T cells that would normally lead the immune attack. It is a communication breakdown that allows the cancer to build a protective shield before it fully forms.

Michela Perego, Ph.D., a research assistant professor in the Altieri lab and first author of the study, explained the significance of these findings. She noted that the immune system and cancers have long been known to communicate. This communication has led to transformative therapies for diseases once thought untreatable. This new research reveals that cancer is also communicating with the nervous system. For a cancer that currently lacks effective therapeutic options, this opens a new door. The team used a mouse model to observe these activities before cancer developed. They observed the excessive amount of NMU. By blocking the communication between the destructive NMUs working for NEPC, they were able to disarm them. This action allowed the T cells to return to the prostate. It reinforced the anti-tumor immune response and restored sensitivity to immunotherapy.