title: 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.
  
  
  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.
authors: Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. h-kato@med.nagoya-cu.ac.jp
authors: Hiroshi
authors: H
authors: Kato
authors: Chiyo
authors: C
authors: Saito
authors: Erika
authors: E
authors: Ito
authors: Takuya
authors: T
authors: Furuhashi
authors: Emi
authors: E
authors: Nishida
authors: Takashi
authors: T
authors: Ishida
authors: Ryuzo
authors: R
authors: Ueda
authors: Hiroshi
authors: H
authors: Inagaki
authors: Akimichi
authors: A
authors: Morita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001494:Baths / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008730:Methoxsalen / Q000627:therapeutic use*; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011701:PUVA Therapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D054398:Receptors, CCR4 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: C515354:CCR4 protein, human; D017319:Photosensitizing Agents; D054398:Receptors, CCR4; D008730:Methoxsalen