PhD defence S. (Sandrine) Nugteren

Summary:

The intestine is continuously exposed to large amounts of bacteria (the commensal microbiota), which are harmless and essential for the development and function of the intestine. The protein Secretory Leukocyte Protease Inhibitor (SLPI) is produced mainly by epithelial cells and has many different functions, including regulation of the innate immune response. In this thesis we investigated whether SLPI expression is increased in the intestinal epithelium of patients with Inflammatory Bowel Disease (IBD) and whether SLPI could classify IBD patients based on the underlying immune response. We found that high colonic epithelial SLPI expression identifies pediatric IBD patients with active clinical disease and strong immune activation. Moreover, high colonic epithelial SLPI expression was associated with previously identified immune profiles related to therapy resistance in IBD, suggesting that SLPI could aid in the identification of IBD patients with therapy nonresponse.  In addition, we questioned whether SLPI expression is increased in colorectal cancer (CRC). We found that high SLPI expression in CRC liver metastases is associated with poor prognosis after resection of liver metastases, suggesting that detection of SLPI protein expression could aid in predicting prognosis in CRC patients with metastatic disease.