Expression und Funktion des Chemokin-Rezeptors CXCR6 auf polymorphkernigen neutrophilen Granulozyten (PMN) — ein lokales Ereignis im Pankreaskarzinom und in akuten Infekten

Abstract

Background: Pancreatic cancer is accompanied by a massive local immune reaction. Chemokine-receptors play a pivotal role in chemotaxis of infiltrating immune cells. Also, in bacterial infections, there is a massive accumulation, especially of PMN. Methods: CD66b and CXCR6 immunofluorescence of tissue of PDAC patients and confocal microscopy were used to identify CXCR6 on infiltrating PMN. Using peripheral blood PMN of PDAC-patients and healthy donors and infiltrating PMN in wound drainages of patients with acute bacterial infections, FACS-analysis was performed to prove CXCR6 expression. Donor PMN were incubated with small concentrations of TNFα and CXCR6 expression was detected using FACS. Chemotaxis-assays in Boyden-chambers were performed after PMN were incubated with CXCL16, which is the single-known ligand of CXCR6, as well as with supernatants of CXCL16 producing pancreatic cancer cells and supernatants of ADAM10 siRNA transfected tumor cells. Results: Local infiltrating PMN in pancreatic cancer tissue showed a distinct CXCR6 expression. In preoperatively collected blood and in blood of healthy controls, no significant CXCR6 expression on PMN was detected. Half of the PMN in wound drainages of patients with acute localized infections were CXCR6 positive; however, only a small number of peripheral blood PMN were CXCR6 positive on the day of surgery or on postoperative day 7. PMN exposition with various concentrations of CXCL16 caused chemotaxis. Conclusion: PMN are present in pancreatic cancer tissue and local bacterial infections. Local mediators caused an upregulation of the expression of CXCR6 on local infiltrating PMN compared to peripheral blood, leading to an increased migration of PMN. This effect might play a role in a tumor-immune-cell interaction of CXCL16 producing tumors or an immune-response in acute localized infections.