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.

• Authors: Hiroshi Kato, Chiyo Saito, Erika Ito, Takuya Furuhashi, Emi Nishida, Takashi Ishida, Ryuzo Ueda, Hiroshi Inagaki, Akimichi Morita
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 13 Issue 3 Pg. 273-80 (Jun 2013) ISSN: 2152-2669 [Electronic] United States
• PMID: 23332394 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• CCR4 protein, human
• Photosensitizing Agents
• Receptors, CCR4
• Methoxsalen

Topics

• Adult
• Aged
• Aged, 80 and over
• Baths (methods)
• Female
• Humans
• Immunohistochemistry
• Male
• Methoxsalen (therapeutic use)
• Middle Aged
• Mycosis Fungoides (drug therapy, immunology, metabolism, therapy)
• PUVA Therapy (methods)
• Photosensitizing Agents (therapeutic use)
• Receptors, CCR4 (biosynthesis, immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)