Increased Immune Cell Activity Linked to Duodenal Cancer Risk in Genetic Disorder

Recent research conducted by scientists at the University Hospital of Bonn has revealed a significant association between the presence of certain immune cells and the increased risk of duodenal cancer in patients with familial adenomatous polyposis (FAP), a hereditary condition that predisposes individuals to bowel cancer.

FAP is characterized by the development of numerous polyps in the colon and rectum, which can lead to cancer if not monitored and managed effectively. Currently, the standard approach for FAP patients involves regular endoscopic surveillance to detect and remove these polyps before they can become cancerous. However, this method does not directly address the underlying risk factors associated with duodenal cancer, which is also heightened in FAP patients.

Dr. Benjamin Krämer, a leading researcher in this study, emphasizes the variability in disease severity seen in different individuals carrying the same genetic mutations, indicating a need to explore additional factors influencing disease progression. The local immune response has emerged as a crucial area of investigation.

The study identifies a notable increase in type 3 innate lymphoid cells (ILC3) within the duodenal tissues of FAP patients. These cells, which play a pivotal role in the body's innate immune system, were found in elevated numbers, particularly around polyps and cancerous lesions. The researchers discovered that these ILC3 cells secrete a protein called interleukin-17A (IL-17A), which is known to affect cellular behavior in the intestines.

Dr. Kim Melanie Kaiser, the primary author of the study, explains that IL-17A seems to encourage intestinal cells to produce harmful molecules known as reactive oxygen species (ROS). These ROS can inflict damage on the genetic material of the cells, a process that is linked to the development of cancer.

The findings suggest that the accumulation of IL-17A-producing ILC3 in the duodenum creates an environment conducive to cancer progression in FAP patients. Prof. Dr. Jacob Nattermann, another co-lead author, states that targeting these immune cells or inhibiting IL-17A production could offer a novel preventive strategy for duodenal cancer in FAP patients, potentially supplementing the standard practice of endoscopic monitoring.

This research, published in Nature Communications, highlights the importance of understanding the immune landscape within the duodenum of FAP patients and opens avenues for new therapeutic interventions aimed at reducing cancer risk.