ECP mediated monocyte to DC differentiation

Extracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T cell lymphoma, graft versus host disease and allografted organ rejection. Its clinical and experimental efficacy in both cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the dendritic antigen presenting cell (DC) differentiation pathway, as determined by expression of relevant genes. The resulting DC are capable of processing and presentation of exogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of co-stimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome indicates that activation or suppression of more than 3500 genes produces a reproducible distinctive molecular signature. Pathway analysis suggests that DC maturation may be triggered by transient adherence of passaged monocytes to plasma proteins coating the ECP plastic ultraviolet exposure plate. Co-incubation with lymphocytes, simultaneously induced by ECP to undergo apoptosis, may accelerate conversion of monocytes to DC. The efficiency with which ECP induces new functional DC supports the possibility that these cells participate prominently in the clinical successes of the treatment. ECP may offer a practical source of DC for use in a spectrum of immunotherapeutic trials. We have used microarrays to analyze the expression of genes modulated by ECP treatment. Samples were obtained pre-treatment, after ECP on day 0 and after overnight incubation of the ECP product on 3 cutaneous T cell lymphoma patients, 3 graft-versus host disease patients and 6 normals.