A Rational Approach to the Therapy of Cutaneous T–Cell Lymphomas

Dummer, Reinhard; Häffner, Andreas C.; Hess, Mark A.; Burg, Günter

doi:10.1159/000218803

Cited by 24 publications

(12 citation statements)

References 18 publications

(21 reference statements)

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“…4 IFN-␣, alone or in combination with retinoids or psoralen plus ultraviolet A irradiation, is helpful, especially in early disease. 5 Interferons are known for their pleiotropic effects. Besides the up-regulation of major histocompatibility complex molecules and the inhibition of cell proliferation and tumor growth, IFN can induce resistance to viral replication in all cells.…”

Section: Introductionmentioning

confidence: 99%

Interferon resistance of cutaneous T-cell lymphoma–derived clonal T-helper 2 cells allows selective viral replication

Dummer

Döbbeling

Geertsen

et al. 2001

Blood

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IntroductionPrimary cutaneous lymphomas are the second most common group of extranodal non-Hodgkin lymphomas after primary gastrointestinal lymphomas. 1 They have highly characteristic clinical features and are considered prototype malignancies because they can be recognized clinically very early. In addition, because of their locations, they are well accessible for the study of immune and molecular biology. Most cutaneous lymphomas are low-grade T-cell lymphomas such as mycosis fungoides and Sézary syndrome (SS). 2 These neoplasms are not curable, even using aggressive chemotherapy and radiotherapy. 3 The malignant lymphocytes mostly express the T-cell markers CD2, CD3, CD4, and CD5. Often they lack CD7, and they display T-helper 2 (Th2) cytokines such as IL-5 and IL-10 and express the IFN-␥ receptor chain 2 (IFN␥R2). 4 IFN-␣, alone or in combination with retinoids or psoralen plus ultraviolet A irradiation, is helpful, especially in early disease. 5 Interferons are known for their pleiotropic effects. Besides the up-regulation of major histocompatibility complex molecules and the inhibition of cell proliferation and tumor growth, IFN can induce resistance to viral replication in all cells. 6 Interferons exert their effects by inducing overlapping sets of effector proteins through specific cell surface receptors (IFN␣R and IFN␥R). In this context, a cross-talk between IFN-␥ and IFN-␣/␤ signaling components has been reported recently. 7 It has been shown that the IFN␣R1 chain favors the association of the IFN␥R1 and the IFN␥R2 chains.Because of the beneficial clinical impact of IFN-␣ and the inhibitory potential of IFN-␥ on benign human and murine Th2 lymphocytes, 8 we studied the effects of IFNs on CTCL-derived tumor cells purified by FACS-sorting from the peripheral blood of 4 patients with SS. 4 This subtype of cutaneous T-cell lymphoma is characterized by an accumulation of malignant T-lymphocytes in skin and peripheral blood. 2 Furthermore, we evaluated the susceptibility of these SS cells to viral infections with vesicular stomatitis virus (VSV). Patients and methods PatientsSS was diagnosed using standard clinical criteria (erythroderma, lymphadenopathy), histologic criteria (subepidermal lymphoid infiltrate showing strong epidermotropism and expressing a T-helper cell phenotype), hematologic criteria (more than 1000 SS cells/mL), and an elevated CD4-CD8 ratio. 9-12 All patients were seronegative for human T-cell lymphocytic virus-I antibodies by enzyme-linked immunosorbent assay. Of the 4 patients whose T-cell clones were identified and investigated, 2 were in stage III (T 4 N 1 M 0) and 2 were in stage IVa (T 4 N 3 M 0 ) disease. 13 They did not receive any systemic therapy in the last 4 weeks before blood was taken. However, topical steroids had to be applied to control itching.Molecular biology studies for the T-cell receptor ␥ chain, 14 Southern blot analysis, or both documented the presence of a dominant T-cell clone in the peripheral blood of all patients. In all patients, a dominant CD4 ϩ V␤ ϩ (do...

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Section: Introductionmentioning

confidence: 99%

Interferon resistance of cutaneous T-cell lymphoma–derived clonal T-helper 2 cells allows selective viral replication

Dummer

Döbbeling

Geertsen

et al. 2001

Blood

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“…Therapeutic approaches include stage-dependent selection of PUVA (psoralen and ultra violet A), retinoids, interferon ␣-2a in combination with acitretin or PUVA (5)(6)(7)(8), various immunomodulators (9), electron radiation (10), or extracorporeal photopheresis (11). These methods are successful in early, but not in the aggressive, later stages of the disease.…”

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confidence: 99%

Serological detection of cutaneous T-cell lymphoma-associated antigens

Eichmüller¹

2001

Proceedings of the National Academy of Sciences

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Cutaneous T-cell lymphomas (CTCL) are a group of skin neoplasms that originate from T lymphocytes and are difficult to treat in advanced stages. The present study is aimed at the identification of tumor-specific antigens from a human testis cDNA library using human sera known as the SEREX (serological identification of recombinantly expressed genes) approach. A cDNA library from normal testicle tissue was prepared and approximately 2 million recombinants were screened with sera from Sé zary Syndrome and Mycosis fungoides patients. A total of 28 positive clones belonging to 15 different genes͞ORFs were identified, including five hitherto unknown sequences. Whereas control sera did not react with most clones, 11-71% sera from CTCL patients were reactive against the identified clones. Expression analysis on 28 normal control and 17 CTCL tissues by reverse transcription-PCR (RT-PCR) and Northern blotting revealed seven ubiquitously distributed antigens, six differentially expressed antigens (several normal tissues were positive), and two tumor-specific antigens that were expressed only in testis and tumor tissues: (i) A SCP-1-like sequence, which has already been detected in various tumors, has been found in one CTCL tumor and four sera of CTCL patients reacted with various SCP-1-like clones and (ii) a new sequence named cTAGE-1 (CTCLassociated antigen 1) was detected in 35% of CTCL tumor tissues and sera of 6͞18 patients reacted with this clone. The present study unravels CTCL-associated antigens independent of the T-cell receptor. The SCP-1-like gene and cTAGE-1 were shown to be immunogenic and immunologically tumor-specific and may therefore be candidates for immunotherapy targeting CTCL. mycosis fungoides ͉ Sé zary Syndrome ͉ SEREX ͉ cancer-testis-antigen ͉ tumor immunology

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“…In the overall analysis, there was no impact of aggressive treatment on disease-free or overall survival [18]. Therefore, a rather mild stage-adapted therapy is recommended for MF [19]. In early stages, local treatment approaches such as topical steroids, PUVA (psoralen plus UVA), locally applied cytostatic drugs such as mechlorethamine [20], BCNU [21], electron beam radiotherapy, or soft X-ray therapy [19] can be used.…”

Section: Therapy Of Cutaneous T-cell Lymphomas (Ctcl) Mycosis Fungoidmentioning

confidence: 99%

Therapy of Cutaneous Lymphoma – Current Practice and Future Developments

et al. 2003

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Cutaneous lymphomas include various types of clonal lymphoproliferative disorders. The adequate treatment approach depends on the exact diagnosis and should be non-aggressive in most cases. In early stages, local approaches such as UV or radiotherapy are preferred. In advanced stages, systemic drugs such as interferon-α or bexarotene can be administered. Experimental approaches for cutaneous lymphomas include vaccination and gene therapy.

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A Rational Approach to the Therapy of Cutaneous T–Cell Lymphomas

Cited by 24 publications

References 18 publications

Interferon resistance of cutaneous T-cell lymphoma–derived clonal T-helper 2 cells allows selective viral replication

Interferon resistance of cutaneous T-cell lymphoma–derived clonal T-helper 2 cells allows selective viral replication

Serological detection of cutaneous T-cell lymphoma-associated antigens

Therapy of Cutaneous Lymphoma – Current Practice and Future Developments

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