Background/Purpose We previously reported that myeloid dendritic cells (mDC) were increased in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) following extracorporeal photopheresis (ECP) using the Therakos UVAR XTS (TM) system. We now assessed monocyte-derived mDCs (Mo-DCs) in L-CTCL patients treated with the CELLEXTM photopheresis system. CD209, a transmembrane receptor, was used to define Mo-DCs. Methods Peripheral blood samples from baseline pre-ECP and at Day 2, 1 month, 3 months, and 6 months post-ECP were analyzed by flow cytometry for Lin(-)HLA-DR(+)CD123(+) plasmacytoid dendritic cells (pDCs), Lin(-)HLA-DR(+)CD11c(+) mDCs, and CD209(+) mDCs. The expression of CD209 mRNA was assessed by real-time PCR. Results At baseline, 7 of 19 patients had lower than normal mDCs, and all patients had lower than normal CD209(+) mDCs in peripheral blood mononuclear cells (0.005% in patients, n = 19, vs 0.50% in healthy donors, n = 7, P < .0001). The CD209(+) mDC numbers only accounted for 3.28% out of total mDCs in patients compared with 66.51% in healthy donors. After treatment, the CD209(+) mDC numbers showed increasing trends in patients. The average absolute numbers of CD209(+) mDCs went up by 4.8-fold at 3 months (n = 10, P = .103) and by 6.4-fold at 6 months (n = 9, P = .100). CD209 mRNA expression went up in two patients responsive to therapy, parallel to CD209(+) mDC numbers. L-CTCL patients achieved 70% overall clinical response rate (7/10) following ECP therapy with the CELLEXTM system. Conclusions Our results suggest that the CELLEXTM photopheresis system is effective for treating L-CTCL patients like the UVAR XTS (TM) system, and in vivo-generated Mo-DCs increase following ECP.

Our previous study found that numbers of myeloid dendritic cells (mDC) and their HLA-DR expression were increased after extracorporeal photopheresis (ECP) in patients with leukemic cutaneous T-cell lymphoma (L-CTCL). To further define the subset of ECP-affected mDCs, we assessed the expression of CD209 on mDCs in L-CTCL patients over a 6-month ECP treatment course. It is known that CD209 or DC-SIGN, a transmembrane receptor, is dominantly expressed on monocyte-derived mDCs (Mo-mDC), and can be used as a biomarker for Mo-mDCs. Nineteen L-CTCL patients who started ECP therapy with the CELLEX photopheresis system were enrolled in the study. The peripheral blood was collected at baseline, at Day 2, 1-month, 3-months, and 6-months after initial ECP treatment, and mDC populations as well as CD209+ mDC subsets were assessed by multi-color flow cytometry. At baseline, about one third of patients showed a low number of mDCs, but all patients had lower than normal CD209+ mDC counts. The average number of CD209+ mDCs was 0.064% out of peripheral blood mononuclear cells (PBMC) in normal donors (n=3), but only 0.006% out of PBMCs in patients (n=19, p<0.05). The CD209+ mDC subset accounts for about 66.2% of total mDCs in normal donors compared to only 13.9% in patients (p<0.05). Eight patients finished 3 and/or 6-month treatment, with 5 clinical responders and 3 non-responders. The average absolute CD209+ mDC counts were increased by about 3-fold at 3-months and 2-fold at 6-months. The average percentages of CD209+ mDCs of PBMCs went up from 0.008% at baseline to 0.015% at 3 months and remained the same at 6 months. Our results suggest that patients with L-CTCL have a deficiency in monocyte-derived myeloid dendritic cells which may be attributed to the suppressed immunity. ECP may exert a positive effect on monocyte-derived myeloid dendritic cells, which might enhance antigen processing and improve anti-tumor immunity in patients with L-CTCL.