Extracorporeal photopheresis (ECP) is a UVA-based phototherapy of whole blood and well established as a first line or combination therapy for the treatment of cutaneous T-cell lymphoma, systemic sclerosis, graft-versus-host disease and is used to control organ transplant rejection. While the proapoptotic activity on activated T-cells is evident, the clinical efficacy of this treatment also appears to be based on other yet unknown mechanisms. In this study, we aimed to identify novel mechanisms of ECP regardless of the patient's background situation. Main

To better understand the immediate consequences of ECP, we analyzed blood plasma of patients with different ECP indications immediately before and after treatment with regard to proteins and lipid mediators. Key findings: While proteome profiling identified substantial inter-individual differences in the protein composition, no significant alteration was detectable upon treatment. In contrast, several fatty acids and lipid mediators were found to be significantly altered by ECP. Remarkably, upregulated lipid mediators including polyunsaturated fatty acids, 12-HEPE and 13-OxoODE have been described to be anti-inflammatory, while the downregulated molecules sphingosine-1-phosphate (S1P) and stearic acid are potent pro-inflammatory mediators. A selective sphingosine-1-phosphate-1 receptor (S1P1) modulator AUY954, which decreases S1P1 and experimentally reduces transplant rejection in vivo, showed greater anti-proliferative activity in human lung fibroblasts from COPD patients compared to normal lung fibroblasts, confirming that this pathway may be important in ECP and its mode of action. Significance and outlook: In