The effect of extracorporeal photopheresis alone or in combination therapy on circulating CD 4 + Foxp3 + CD 25 − T cells in patients with leukemic cutaneous T‐cell lymphoma

Purpose Extracorporeal photopheresis ( ECP ) alone or in combination therapy is effective for treatment of leukemic cutaneous T‐cell lymphoma ( L‐CTCL ), but its mechanism(s) of action remain unclear. This study was designed to investigate the effect of ECP on regulatory T cells and CD8 + T cells in L‐CTCL patients. Experimental Design Peripheral blood from 18 L‐CTCL patients at baseline, Day 2, 1 month, 3 month, and 6 month post‐ECP therapy was analyzed by flow cytometry for CD4 + CD25 +/high , CD4 + Foxp3 + CD25 +/− , CD3 + CD8 + , CD3 + CD8 + CD69 + , and CD3 + CD8 + IFN‐γ + T cells. Clinical responses were assessed and correlated with changes in these T‐cell subsets. Results Twelve of 18 patients achieved clinical responses. The average baseline number of CD4 + CD25 +/high T cells of PBMCs in L‐CTCL patients was normal (2.2%), but increased at 6‐month post‐therapy (4.3%, P  < 0.01). The average baseline number of CD4 + Foxp3 + T cells out of CD4 + T cells in nine evaluable patients was high (66.8 ± 13.7%), mostly CD25 negative. The levels of CD4 + Foxp3 + T cells in responders were higher ( n  = 6, 93.1 ± 5.7%) than nonresponders ( n  = 3, 14.2 ± 16.0%, P  < 0.01), and they declined in parallel with malignant T cells. The numbers of CD3 + CD8 + CD69 + and CD3 + CD8 + IFN‐γ + T cells increased at 3‐month post‐therapy in five of six patients studied. Conclusions Extracorporeal photopheresis alone or in combination therapy might be effective in L‐CTCL patients whose malignant T cells have a CD4 + Foxp3 + CD25 − phenotype.