Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy

• Published in: Blood 2010-12, Vol.116 (23), p.4838-4847
• Main Authors: Berger, Carole, Hoffmann, Kristin, Vasquez, Juan G., Mane, Shrikant, Lewis, Julia, Filler, Renata, Lin, Aiping, Zhao, Hongyu, Durazzo, Tyler, Baird, Abigail, Lin, William, Foss, Francine, Christensen, Inger, Girardi, Michael, Tigelaar, Robert, Edelson, Richard
• Format: Article
• Language: English
• Subjects: Antigen Presentation - drug effects; Antigen Presentation - physiology; Antigen Presentation - radiation effects; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - radiation effects; Cell Separation; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - radiation effects; Flow Cytometry; Gene Expression - drug effects; Gene Expression - radiation effects; Graft vs Host Disease - immunology; Hematologic and hematopoietic diseases; Humans; Immunobiology; Immunophenotyping; In Situ Hybridization; Lymphoma, T-Cell, Cutaneous - immunology; Medical sciences; Monocytes - cytology; Oligonucleotide Array Sequence Analysis; Photopheresis; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-11-256040

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 cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the antigen-presenting dendritic cell (DC) differentiation pathway, within a single day, without added cytokines, as determined by enhanced expression of relevant genes. The resulting DCs are capable of processing and presentation of exogenous and endogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of costimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome reveals that activation or suppression of more than 1100 genes produces a reproducible distinctive molecular signature, common to ECP-processed monocytes from normal subjects, and those from patients. Because ECP induces normal monocytes to enter the DC differentiation pathway, this phenomenon is independent of disease state. The efficiency with which ECP stimulates new functional DCs supports the possibility that these cells participate prominently in the clinical successes of the treatment. Appropriately modified by future advances, ECP may potentially offer a general source of therapeutic DCs.