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Individuals diagnosed with familial adenomatous polyposis (FAP) face a significantly heightened risk of developing malignant tumors in the duodenum. Recent research led by scientists at the University Hospital Bonn and the Cluster of Excellence ImmunoSensation2 has uncovered a mechanism within the local immune system that may facilitate cancer development. This discovery presents a new frontier in the prevention of duodenal carcinoma among FAP patients, with the findings recently published in Nature Communications.
Familial adenomatous polyposis is a genetic disorder linked not only to a markedly increased risk of colorectal cancer but also to a notable risk of cancer in the duodenum. Currently, management of this condition primarily involves vigilant endoscopic monitoring and the removal of precursors, known as polyps. However, this approach carries its own risks. “Presently, there are no targeted preventive therapies,” states Dr. Benjamin Krämer, co-lead author and Scientific Head of the Laboratory for Congenital Cellular Immunology at the UKB. “Given the wide variation in disease severity among individuals with the same genetic mutation, our research is focused on identifying additional factors that influence disease progression, particularly elements of the local immune system.”
Neurotransmitter linked to genetic damage
The team at Bonn has identified that certain innate immune cells, known as type 3 innate lymphoid cells (ILC3), are present in elevated numbers within the duodenal tissue of FAP patients. “We observed a significant increase of these cells in the mucosal layer, especially around polyps and areas affected by cancer,” explains Dr. Robert Hüneburg, co-lead author and senior physician at the Medical Clinic I and the National Center for Hereditary Tumor Diseases at UKB.
This research sheds light on the potential role these immune cells play in cancer development: they secrete a neurotransmitter called interleukin-17A (IL-17A). “IL-17A appears to encourage intestinal cells to generate harmful compounds referred to as reactive oxygen species (ROS). Elevated levels of ROS can inflict damage on cellular genetic material,” notes Dr. Kim Melanie Kaiser, the first author of the study and former doctoral researcher in the ImmunoSensation² Cluster of Excellence. Such DNA damage has been established as a contributing factor to cancer progression.
According to Prof. Dr. Jacob Nattermann, another co-lead author, “The increased prevalence of IL-17A-producing ILC3 cells in the duodenum creates a localized environment that may favor cancer development in individuals with FAP.” He serves as the Deputy Director of Medical Clinic I and a senior physician at the National Center for Hereditary Tumor Diseases. He is also part of the Cluster of Excellence ImmunoSensation² and the Transdisciplinary Research Area “Life & Health” at the University of Bonn. “Intervening in the activity of these immune cells or, specifically, obstructing IL-17A in the duodenum could emerge as a promising strategy to prevent duodenal cancer in FAP patients, providing a crucial alternative to exclusive endoscopic surveillance.”
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