Skip to main content
Top
Published in: International Journal of Hematology 4/2014

01-04-2014 | Original Article

Narrowband ultraviolet B phototherapy ameliorates acute graft-versus-host disease by a mechanism involving in vivo expansion of CD4+CD25+Foxp3+ regulatory T cells

Authors: Satoshi Iyama, Kazuyuki Murase, Tsutomu Sato, Akari Hashimoto, Ayumi Tatekoshi, Hiroto Horiguchi, Yusuke Kamihara, Kaoru Ono, Shohei Kikuchi, Kohichi Takada, Yutaka Kawano, Tsuyoshi Hayashi, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Satoru Mori, Junji Kato, Toshiharu Yamashita, Junji Kato

Published in: International Journal of Hematology | Issue 4/2014

Login to get access

Abstract

Narrowband ultraviolet B phototherapy (NB-UVB) is a therapeutic alternative for haematopoietic stem cell transplantation-related skin graft-versus-host disease (GVHD). The beneficial effects of this intervention may be induced by direct irradiation of inflammatory cells in the skin; however, the putative involvement of indirect effects on systemic immunity has not been elucidated. To address this issue, 11 acute skin GVHD patients refractory to standard corticosteroid treatment and with no gut/liver involvement were treated with NB-UVB irradiation. The median number of treatments was 10 times, with a mean cumulative exposure of 6.36 J/cm2. No other immunosuppressive therapy was initiated during irradiation. Eight patients achieved an objective complete response, two had a partial response, and one showed no change. None of the patients experienced progressive skin GVHD or newly diagnosed gut/liver GVHD. NB-UVB was well tolerated, with no patients discontinuing irradiation due to toxicity. We additionally demonstrated by flow cytometry that NB-UVB irradiation induces the increment of the proportion of regulatory T cell (Tregs) in patients’ peripheral blood. These results suggest that NB-UVB may exert beneficial effects on steroid-refractory skin GVHD through the expansion of Tregs.
Appendix
Available only for authorised users
Literature
2.
go back to reference Barrett J. Graft-versus-host disease. In: Barrett AJ, Treleaven J, editors. Bone marrow transplantation in practice. Edinburgh: Churchill Linvingstone; 1992. p. 257. Barrett J. Graft-versus-host disease. In: Barrett AJ, Treleaven J, editors. Bone marrow transplantation in practice. Edinburgh: Churchill Linvingstone; 1992. p. 257.
3.
go back to reference Klingebiel T, Schlegel PG. GVHD: overview on pathophysiology, incidence, clinical and biological features. Bone Marrow Transplant. 1998;21(Suppl 2):S45–9.PubMed Klingebiel T, Schlegel PG. GVHD: overview on pathophysiology, incidence, clinical and biological features. Bone Marrow Transplant. 1998;21(Suppl 2):S45–9.PubMed
4.
go back to reference Weisdorf D, Haake R, Blazar B, Miller W, McGlave P, Ramsay N, et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood. 1990;75:1024–30.PubMed Weisdorf D, Haake R, Blazar B, Miller W, McGlave P, Ramsay N, et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood. 1990;75:1024–30.PubMed
5.
go back to reference Martin PJ, Schoch G, Fisher L, Byers V, Anasetti C, Appelbaum FR, et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood. 1990;76:1464–72.PubMed Martin PJ, Schoch G, Fisher L, Byers V, Anasetti C, Appelbaum FR, et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood. 1990;76:1464–72.PubMed
6.
go back to reference Teshima T, Ferrara JL. Understanding the alloresponse: new approaches to graft-versus-host disease prevention. Semin Hematol. 2002;39:15–22.PubMedCrossRef Teshima T, Ferrara JL. Understanding the alloresponse: new approaches to graft-versus-host disease prevention. Semin Hematol. 2002;39:15–22.PubMedCrossRef
7.
go back to reference Ferrara JL, Levy R, Chao NJ. Pathophysiologic mechanisms of acute graft-vs.-host disease. Biol Blood Marrow Transplant. 1999;5:347–56.PubMedCrossRef Ferrara JL, Levy R, Chao NJ. Pathophysiologic mechanisms of acute graft-vs.-host disease. Biol Blood Marrow Transplant. 1999;5:347–56.PubMedCrossRef
8.
go back to reference Martin PJ, Schoch G, Fisher L, Byers V, Appelbaum FR, McDonald GB, et al. A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment. Blood. 1991;77:1821–8.PubMed Martin PJ, Schoch G, Fisher L, Byers V, Appelbaum FR, McDonald GB, et al. A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment. Blood. 1991;77:1821–8.PubMed
9.
go back to reference Hymes SR, Morison WL, Farmer ER, Walters LL, Tutschka PJ, Santos GW. Methoxsalen and ultraviolet A radiation in treatment of chronic cutaneous graft-versus-host reaction. J Am Acad Dermatol. 1985;12:30–7.PubMedCrossRef Hymes SR, Morison WL, Farmer ER, Walters LL, Tutschka PJ, Santos GW. Methoxsalen and ultraviolet A radiation in treatment of chronic cutaneous graft-versus-host reaction. J Am Acad Dermatol. 1985;12:30–7.PubMedCrossRef
10.
go back to reference Vogelsang GB, Wolff D, Altomonte V, Farmer E, Morison WL, Corio R, et al. Treatment of chronic graft-versus-host disease with ultraviolet irradiation and psoralen (PUVA). Bone Marrow Transplant. 1996;17:1061–7.PubMed Vogelsang GB, Wolff D, Altomonte V, Farmer E, Morison WL, Corio R, et al. Treatment of chronic graft-versus-host disease with ultraviolet irradiation and psoralen (PUVA). Bone Marrow Transplant. 1996;17:1061–7.PubMed
11.
go back to reference Furlong T, Leisenring W, Storb R, Anasetti C, Appelbaum FR, Carpenter PA, et al. Psoralen and ultraviolet A irradiation (PUVA) as therapy for steroid-resistant cutaneous acute graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8:206–12.PubMedCrossRef Furlong T, Leisenring W, Storb R, Anasetti C, Appelbaum FR, Carpenter PA, et al. Psoralen and ultraviolet A irradiation (PUVA) as therapy for steroid-resistant cutaneous acute graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8:206–12.PubMedCrossRef
12.
go back to reference Grundmann-Kollmann M, Martin H, Ludwig R, Klein S, Boehncke WH, Hoelzer D, et al. Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease. Transplantation. 2002;74:1631–4.PubMedCrossRef Grundmann-Kollmann M, Martin H, Ludwig R, Klein S, Boehncke WH, Hoelzer D, et al. Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease. Transplantation. 2002;74:1631–4.PubMedCrossRef
13.
go back to reference Feldstein JV, Bolanos-Meade J, Anders VL, Abuav R. Narrowband ultraviolet B phototherapy for the treatment of steroid-refractory and steroid-dependent acute graft-versus-host disease of the skin. J Am Acad Dermatol. 2011;65:733–8.PubMedCentralPubMedCrossRef Feldstein JV, Bolanos-Meade J, Anders VL, Abuav R. Narrowband ultraviolet B phototherapy for the treatment of steroid-refractory and steroid-dependent acute graft-versus-host disease of the skin. J Am Acad Dermatol. 2011;65:733–8.PubMedCentralPubMedCrossRef
14.
go back to reference Coimbra S, Oliveira H, Reis F, Belo L, Rocha S, Quintanilha A, et al. Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy. Br J Dermatol. 2010;163:1282–90.PubMedCrossRef Coimbra S, Oliveira H, Reis F, Belo L, Rocha S, Quintanilha A, et al. Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy. Br J Dermatol. 2010;163:1282–90.PubMedCrossRef
15.
go back to reference Shin HJ, Baker J, Leveson-Gower DB, Smith AT, Sega EI, Negrin RS. Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4+CD25+Foxp3+ regulatory T cells. Blood. 2011;118:2342–50.PubMedCrossRef Shin HJ, Baker J, Leveson-Gower DB, Smith AT, Sega EI, Negrin RS. Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4+CD25+Foxp3+ regulatory T cells. Blood. 2011;118:2342–50.PubMedCrossRef
16.
go back to reference Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365:2055–66.PubMedCentralPubMedCrossRef Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365:2055–66.PubMedCentralPubMedCrossRef
17.
go back to reference Ngoma AM, Ikeda K, Hashimoto Y, Mochizuki K, Takahashi H, Sano H, et al. Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation. Int J Hematol. 2012;95:86–94.PubMedCrossRef Ngoma AM, Ikeda K, Hashimoto Y, Mochizuki K, Takahashi H, Sano H, et al. Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation. Int J Hematol. 2012;95:86–94.PubMedCrossRef
18.
go back to reference Westin JR, Saliba RM, De Lima M, Alousi A, Hosing C, Qazilbash MH, et al. Steroid-refractory acute GVHD: predictors and outcomes. Adv Hematol. 2011;2011:601953.PubMedCentralPubMedCrossRef Westin JR, Saliba RM, De Lima M, Alousi A, Hosing C, Qazilbash MH, et al. Steroid-refractory acute GVHD: predictors and outcomes. Adv Hematol. 2011;2011:601953.PubMedCentralPubMedCrossRef
19.
go back to reference Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.PubMedCrossRef Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.PubMedCrossRef
20.
go back to reference Hart JW, Shiue LH, Shpall EJ, Alousi AM. Extracorporeal photopheresis in the treatment of graft-versus-host disease: evidence and opinion. Ther Adv Hematol. 2013;4:320–34.PubMedCentralPubMedCrossRef Hart JW, Shiue LH, Shpall EJ, Alousi AM. Extracorporeal photopheresis in the treatment of graft-versus-host disease: evidence and opinion. Ther Adv Hematol. 2013;4:320–34.PubMedCentralPubMedCrossRef
21.
go back to reference Kreutz M, Karrer S, Hoffmann P, Gottfried E, Szeimies RM, Hahn J, et al. Whole-body UVB irradiation during allogeneic hematopoietic cell transplantation is safe and decreases acute graft-versus-host disease. J Invest Dermatol. 2012;132:179–87.PubMedCrossRef Kreutz M, Karrer S, Hoffmann P, Gottfried E, Szeimies RM, Hahn J, et al. Whole-body UVB irradiation during allogeneic hematopoietic cell transplantation is safe and decreases acute graft-versus-host disease. J Invest Dermatol. 2012;132:179–87.PubMedCrossRef
22.
go back to reference Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003;198:1875–86.PubMedCentralPubMedCrossRef Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003;198:1875–86.PubMedCentralPubMedCrossRef
23.
go back to reference Lee HS, Kooshesh F, Sauder DN, Kondo S. Modulation of TGF-beta 1 production from human keratinocytes by UVB. Exp Dermatol. 1997;6:105–10.PubMedCrossRef Lee HS, Kooshesh F, Sauder DN, Kondo S. Modulation of TGF-beta 1 production from human keratinocytes by UVB. Exp Dermatol. 1997;6:105–10.PubMedCrossRef
24.
go back to reference Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144–50.PubMedCrossRef Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144–50.PubMedCrossRef
25.
go back to reference Larko O. Treatment of psoriasis with a new UVB-lamp. Acta Derm Venereol. 1989;69:357–9.PubMed Larko O. Treatment of psoriasis with a new UVB-lamp. Acta Derm Venereol. 1989;69:357–9.PubMed
Metadata
Title
Narrowband ultraviolet B phototherapy ameliorates acute graft-versus-host disease by a mechanism involving in vivo expansion of CD4+CD25+Foxp3+ regulatory T cells
Authors
Satoshi Iyama
Kazuyuki Murase
Tsutomu Sato
Akari Hashimoto
Ayumi Tatekoshi
Hiroto Horiguchi
Yusuke Kamihara
Kaoru Ono
Shohei Kikuchi
Kohichi Takada
Yutaka Kawano
Tsuyoshi Hayashi
Koji Miyanishi
Yasushi Sato
Rishu Takimoto
Masayoshi Kobune
Satoru Mori
Junji Kato
Toshiharu Yamashita
Junji Kato
Publication date
01-04-2014
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 4/2014
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-014-1530-1

Other articles of this Issue 4/2014

International Journal of Hematology 4/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine