Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy.
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.
Berger
Carole
C
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA. carole.berger@yale.edu
Hoffmann
Kristin
K
Vasquez
Juan G
JG
Mane
Shrikant
S
Lewis
Julia
J
Filler
Renata
R
Lin
Aiping
A
Zhao
Hongyu
H
Durazzo
Tyler
T
Baird
Abigail
A
Lin
William
W
Foss
Francine
F
Christensen
Inger
I
Girardi
Michael
M
Tigelaar
Robert
R
Edelson
Richard
R
D017951:Antigen Presentation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D017403:In Situ Hybridization; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology; D009000:Monocytes / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D017893:Photopheresis; D020133:Reverse Transcriptase Polymerase Chain Reaction