Immunopathogenesis and therapy of cutaneous T cell lymphoma

Kim, Ellen J.; Hess, Stephen D.; Richardson, Stephen K.; Newton, Sara; Showe, Louise C.; Benoit, Bernice M.; Ubriani, Ravi; Vittorio, Carmela C.; Junkins‐Hopkins, Jacqueline M.; Wysocka, Maria; Rook, Alain H.

doi:10.1172/jci24826

Cited by 325 publications

(247 citation statements)

References 122 publications

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“…Topical corticosteroids target the majority of the tumour burden in the skin by directly inducing apoptosis of malignant T cells, and can induce complete clearance of the disease. 4 This treatment also decreases the number of Langerhans cells, thus interrupting the stimulation of malignant T cells. 4 Topical corticosteroids can be used to treat individual skin lesions and are available as lotions, creams or ointments.…”

Section: Topical Corticosteroidsmentioning

confidence: 99%

“…4 This treatment also decreases the number of Langerhans cells, thus interrupting the stimulation of malignant T cells. 4 Topical corticosteroids can be used to treat individual skin lesions and are available as lotions, creams or ointments.…”

Section: Topical Corticosteroidsmentioning

confidence: 99%

“…Approximately two-thirds of these lymphomas are of T-cell origin, and the pathogenesis and management of both T-and B-cell cutaneous lymphomas have been recently reviewed. [1][2][3][4][5][6] The most common form of cutaneous T-cell lymphoma (CTCL) is mycosis fungoides (MF), accounting for around 60% of new cases. Sé zary syndrome (SS) is much rarer and accounts for only 5% of CTCL cases.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

Trautinger

Knobler

Willemze

et al. 2006

European Journal of Cancer

391

308

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Section: Topical Corticosteroidsmentioning

confidence: 99%

Section: Topical Corticosteroidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

Trautinger

Knobler

Willemze

et al. 2006

European Journal of Cancer

391

308

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“…In the later stages, MF lesions gradually form plaques and overt tumors, and eventually involve lymph nodes and internal organs. [1][2][3][4][5] SS is a particular aggressive variant of CTCL with a mean survival of 3 years from the time of diagnosis. The disease is characterized by the presence of circulating lymphocytes with atypical cerebriform nuclei (Sézary cells) in the skin, lymph nodes and peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome

et al. 2008

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Sé zary syndrome (SS) is an aggressive variant of cutaneous T-cell lymphoma. During disease progression, immunodeficiency develops; however, the underlying molecular and cellular mechanisms are not fully understood. Here, we study the regulatory T cell (Treg) function and the expression of FOXP3 in SS. We demonstrate that malignant T cells in 8 of 15 patients stain positive with an anti-FOXP3 antibody. Western blotting analysis shows expression of two low molecular splice forms of FOXP3, but not of wild-type (wt) FOXP3. The malignant T cells produce interleukin-10 and TGF-b and suppress the growth of non-malignant T cells. The Treg phenotype and the production of suppressive cytokines are driven by aberrant activation of Jak3 independent of the FOXP3 splice forms. In contrast to wt FOXP3, the low molecular splice forms of FOXP3 have no inhibitory effect on nuclear factor-jB (NF-jB) activity in reporter assays which is in keeping with a constitutive NF-jB activity in the malignant T cells. In conclusion, we show that the malignant T cells express low molecular splice forms of FOXP3 and function as Tregs. Furthermore, we provide evidence that FOXP3 splice forms are functionally different from wt FOXP3 and not involved in the execution of the suppressive function. Thus, this is the first description of FOXP3 splice forms in human disease.

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“…As CTCL progresses, clonal CD4 T-cells produce increased Type 2 (Th2) cytokines and the production of Type 1 (Th1) helper T-cell cytokines decreases, resulting in decreased cell-mediated cytotoxicity. 2 Therapy is increasingly directed at correcting these cytokine imbalances. [3][4][5] The combined use of retinoids and interferons has been studied in CTCL because of their complementary immunomodulating effects and their nonoverlapping toxicity profiles.…”

mentioning

confidence: 99%

Results of a Phase II trial of oral bexarotene (Targretin) combined with interferon alfa‐2b (Intron‐A) for patients with cutaneous T‐cell lymphoma

Straus

Duvic

Kuzel

et al. 2007

Cancer

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BACKGROUND.Bexarotene is one of the most active single agents for the treatment of recurring or refractory cutaneous T‐cell lymphoma (CTCL). Interferon alfa has also been used for many years as an effective treatment for this disease. The results in recent case reports of the combination of bexarotene and interferon alfa have been promising. Based on more extensive results reported with the combination of other retinoids with interferon alfa, the present study attempted to determine the response rate, response duration, and safety of bexarotene (Targretin capsules, Ligand Pharmaceuticals, San Diego, Calif) alone and then with the addition of interferon alfa‐2b (Intron‐A, Schering‐Plough, Kenilworth, NJ).METHODS.Patients with biopsy‐proven CTCL, TNM stages IB, IIA, IIB‐IV, were treated with oral bexarotene 300 mg/m2/day for at least 8 weeks. If a complete response was not seen after 8 weeks, interferon alfa‐2b 3 million units (MU) subcutaneously was added, and increased to 5 MU if tolerated, 3 times a week.RESULTS.A total of 22 patients were enrolled at 5 sites, and 18 patients were assessable for response. Overall response rate for combined bexarotene and interferon alfa was 39% (95% confidence interval [CI]: 17%–64%), including 1 patient with a clinical complete response, 6 patients with partial response, 3 patients with stable disease, and 8 patients with progressive disease. Three partial responses were first noted during the bexarotene‐alone phase. Adverse events were generally manageable, and only 1 patient was withdrawn from study for hypertriglyceridemia.CONCLUSIONS.The addition of interferon alfa‐2b did not increase the response rate that would have been expected with bexarotene alone. Cancer 2007. © 2007 American Cancer Society.

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Immunopathogenesis and therapy of cutaneous T cell lymphoma

Cited by 325 publications

References 122 publications

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome

Results of a Phase II trial of oral bexarotene (Targretin) combined with interferon alfa‐2b (Intron‐A) for patients with cutaneous T‐cell lymphoma

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