Bath-PUVA Therapy Decreases Infiltrating CCR4-Expressing Tumor Cells and Regulatory T Cells in Patients With Mycosis Fungoides

Abstract Background Mycosis fungoides (MF) is a malignant lymphoma characterized by expansion of CD4 + memory T-cell clones. Infiltrating cells express CCR4, which is attracted to CC chemokine ligands 17 and 22 (thymus and activation-regulated chemokine [TARC]/CCL17 and TARC/CCL22). Bath–psoralen plus ultraviolet A (PUVA) is effective against MF. In patients with psoriasis, bath-PUVA induces circulating regulatory T cells (Tregs), which suppress effector T cells. To understand the mechanisms in MF, we analyzed lesion-infiltrating cells before and after bath-PUVA therapy. Patients and Methods Thirteen patients with MF (12 stage IB, 1 stage III; mean age 69.2 years, range 35-87 years; 6 men, 7 women) were recruited. Results Immunohistochemical analysis revealed that lesion CCR4-positive (CCR4 + ) cells and Tregs significantly decreased from 105.1 ± 164.8 cells/10 −2 mm 2 to 31.4 ± 39.0 cells/10 −2 mm 2 and from 78.1 ± 67.8 cells/10 −2 mm 2 to 24.7 ± 25.0 cells/10 −2 mm 2 , respectively. Serum TARC levels significantly correlated with infiltrating CD3 + ( r = 0.997), CCR4 + ( r = 0.991), and forkhead box P3–positive (Foxp3 +) cells ( r = 0.843). Circulating Tregs before bath-PUVA therapy were not significantly different from those in healthy volunteers. Bath-PUVA did not significantly change the percentage of circulating Tregs. Conclusions Bath-PUVA decreased CCR4 + cells and Tregs in MF lesions but did not induce circulating Tregs, which might suppress effector T cells. Direct effects through skin lesions might eliminate both pathogenetically relevant cells and Tregs. Systemic immunosuppression was not induced.