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  • 1
    Electronic Resource
    Electronic Resource
    IL-15 and IL-16 overexpression in cutaneous T-cell lymphomas: stage-dependent increase in mycosis fungoides progression (2000)
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 9 (2000), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cytokines are of major importance for the pathogenesis of cutaneous T-cell lymphomas (CTCL). Recent data suggested that IL-15 and IL-16 are survival/growth factors for the malignant T cells in these entities. To investigate the expression of IL-15 and IL-16 in mycosis fungoides (MF) and CD30+ pleomorphic T-cell lymphoma in vivo, we established a competitive RT-PCR technique. Analyzing skin biopsies from CTCL patients at different stages in comparison to psoriatic and healthy skin, we found IL-15 and IL-16 mRNA overexpression in both CTCL entities. Remarkably, there was some evidence for a stage-dependent increase during MF progression. We found only slight overexpression in early stage MF, when only few tumor cells are detectable within the infiltrates, whereas marked overexpression was found in more advanced lesions, which are characterized by a higher density of malignant cells. These results suggested that CTCL cells themselves might produce the cytokines. To further elucidate this hypothesis, two CTCL cell lines were analyzed but gave conflicting results. Therefore, the cellular origin of the IL-15 and IL-16 overexpression in CTCL remains unclear. Considering the significant overexpression of IL-15 and IL-16 and their biological capacities it is likely that these cytokines contribute to the tumor development. So, they might be involved in growth and skin homing of CTCL cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0625.2000.009004248.x
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  • 2
    Electronic Resource
    Electronic Resource
    Cytokine expression in primary cutaneous germinal center cell lymphomas (2000)
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 9 (2000), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Physiologically, B-lymphocytes are not present in the skin. Even in pathological situations they rarely occur. In contrast, primary cutaneous B-cell lymphomas (CBCL) are characterized by proliferation of B lymphocytes within the skin. This suggests the existence of a certain microenvironment supporting homing and expansion of clonal B cells. Cytokines were demonstrated to be involved in the pathogenesis of cutaneous lymphomas of T-cell origin. Cytokine expression in cutaneous B-cell lymphoma lesions, however, has not been investigated so far. Therefore, the mRNA level of several cytokines was analyzed in biopsies from 7 patients with CBCL and compared to pleomorphic T-cell lymphoma (n=6), psoriasis (n=9), and healthy skin (n=7), using a competitive RT-PCR approach. An overexpression of TNF-α, IL-10, and IL-6 was found. Enhanced IL-8 mRNA expression was detected in 2/7 cases. The overexpression of IL-6 and IL-10 in CBCL might be of particular importance, since these cytokines are considered to support B-cell growth. Additionally, the overexpression of IL-10 may contribute to tumor progression since this immunosuppressive cytokine might be involved in downregulation of immunological tumor surveillance, in part by inhibiting type 1 cytokine formation. In fact, we did not detect IFN-γ and IL-2 expression. Taken together, we found a cytokine pattern in CBCL lesions which might contribute to tumor B-cell growth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0625.2000.009001071.x
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  • 3
    Electronic Resource
    Electronic Resource
    Systemic eight-cycle anti-CD20 monoclonal antibody (rituximab) therapy in primary cutaneous B-cell lymphomas – an applicational observation (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Primary cutaneous B-cell lymphomas (PCBCLs) are characterized by restriction to the skin and a variable but mostly favourable prognosis. Since 1997 the recombinant, chimeric anti-CD20 antibody rituximab has been used in patients suffering from non-Hodgkin's B-cell lymphomas. Different studies have shown that the effectiveness and safety in the treatment of patients with low-grade follicular lymphoma is comparable to or even higher than the standard CHOP chemotherapy. So far it has been unclear whether an extended duration of therapy leads to a benefit for the patients with PCBCL.Objectives  To evaluate the objective response rate, time to progression, remission quality and histological changes and to compare our data with the literature.Patients/Methods  Ten patients with PCBCL [eight with follicle centre cell lymphoma (FCCL), one with marginal zone lymphoma (MZL) and one with diffuse large B-cell lymphoma of the leg (DLBCL)] were treated by intravenous application of a chimeric antibody against the CD20 transmembrane antigen (rituximab) with a dosage of eight cycles, 375 mg m−2 body surface, weekly.Results  The treatment regimen resulted in clinical overall response in 9 of 10 patients, in particular there were seven complete responses (70%) plus two partial responses (20%). The median duration of remission (durable remission, DR) is 23 months (4–30 months) to date. Histological assessment of responses in four patients showed no tumour-specific infiltration. In two patients histology revealed a residual infiltration and in one patient an increasing infiltration. In two patients no histology was taken after treatment; one patient developed a new lesion. No severe side-effects occurred. Observed side-effects were two bacterial infections, two patients with shivering during infusion, one patient with sweating for months and one patient with persisting itching. As expected the B-cell count in peripheral blood was depressed in all patients after infusion.Conclusions  Intravenous therapy with eight cycles of the anti-CD20 antibody rituximab is a non-toxic and effective treatment for a subset of patients with PCBCL (relapsed, aggressive entity, old patients, multiple lesions) with a long DR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06659.x
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  • 4
    Electronic Resource
    Electronic Resource
    On the possible relationship between staphylococcal superantigens and increased Vβ5·1 usage in cutaneous T-cell lymphoma: reply from authors (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06523.x
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  • 5
    Electronic Resource
    Electronic Resource
    Polyclonal expansion of T cells with the TCR Vβ type of the tumour cell in lesions of cutaneous T-cell lymphoma: evidence for possible superantigen involvement (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 150 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The involvement of superantigens in the pathology of cutaneous T-cell lymphomas (CTCL) has been suggested before, but without unequivocal evidence for superantigen activity in the patients. Seeking evidence for superantigen activity we analysed clones and microdissected single cells isolated from the epidermis of early-stage lesions of a CTCL patient for their T-cell receptor (TCR) Vβ expression and TCR Vγ gene rearrangements. The vast majority of these T cells expressed the TCR Vβ family type of the tumour. From their TCR γ gene rearrangements, however, these cells were polyclonal. The tumour cell clone accounted for about 60% of these cells, about 40% were of heterogeneous origin. This dominance of a single Vβ family in the polyclonally expanded dermal T-cell populations implies superantigen activity in the CTCL lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.05970.x
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  • 6
    Electronic Resource
    Electronic Resource
    A T-cell epitope determined with random peptide libraries and combinatorial peptide chemistry stimulates T cells specific for cutaneous T-cell lymphoma (2000)
    Springer
    Annals of oncology 11 (2000), S. 95-99 
    Details
    ISSN: 1569-8041
    Keywords: cutaneous T-cell lymphoma ; immunotherapy ; peptide library ; T-cell epitope ; tumour-associated antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Mycosis fungoides is the most frequent T-cell lymphomaof the skin. Despite numerous attempts, no tumour antigens have yet beenidentified. Only in one case has an idiotype-derived peptide been found totrigger CTL of the respective patient. The identification of natural antigensrequires the cultivation of large amounts of tumour cells in vitro,which has been possible in two exceptional cases. The identification ofsynthetic epitopes for tumour-specific CTL with random peptide libraries canovercome this limitation and is a powerful tool for application in thedevelopment of immune therapies for a wide range of patients. Materials and methods:The critical amino acids for theconstruction of epitopes for the CTCL-specific CTL clone My-La CTL weredetermined with synthetic peptide libraries in positional scanning OX8 formatin a standard 61chromium release assay. Sixteen different peptidescould be synthesized from the combinatoric of these amino acids with thecanonical anchor amino acids for MHC binding. These peptides were tested fortheir capacity to stimulate My-La CTL and PBMC of an HLA-matched CTCL patient. Results:A synthetic epitope could be identified for My-La CTL,which was recognized in a HLA-restricted manner. The response towards thisepitope was comparable to the response towards their natural target My-La.Using these synthetic epitopes, T cells of a HLA-matched patient could beinduced in vitroand led to the establishment of different cell linesand clones. Some of these lines recognized the peptides as well as theallogenic but HLA-matched tumour cell line My-La, indicating that they arespecific for a naturally expressed tumour antigen. Conclusions:The identification of synthetic epitopes fortumour-specific CTL clones can be used for the development of vaccines forimmune therapies of cancer; such peptides can be applied inter-individually.Synthetic epitopes must not correspond to the natural ones, but they can beeven more potent as stimulation of specific T cells and can be fine-tuned toincrease the success of the therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008395812464
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  • 7
    Electronic Resource
    Electronic Resource
    Kutane B-Zell-Lymphome (2000)
    Springer
    Der Hautarzt 51 (2000), S. 363-375 
    Details
    ISSN: 1432-1173
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Lernziel Primär kutane B-Zell-Lymphome (PCBCL) gehören zur Gruppe der Non-Hodgkin-Lymphome. Die Klassifikation erfolgt entsprechend dem Konsens der EORTC. Ziel dieses Artikels ist es, die wesentlichen klinischen Manifestationsformen und ihre entsprechenden histologischen Merkmale zu vermitteln: häufiger vorkommendes, histologisch vom Typ des Keimzentrumszell-Lymphoms, prognostisch günstiges B-Zell-Lymphom am Stamm und Kopf sowie selten zu diagnostizierendes, prognostisch ungünstiges großzelliges B-Zell-Lymphom der unteren Extremität. Es werden Empfehlungen zum einheitlichen Vorgehen in Staging und Diagnostik gegeben. Die Behandlungsmöglichkeiten der PCBCL sind vielfältig und sollten sich an den klinischen Entitäten sowie deren Prognose orientieren. Sie reichen von Exzision über Radiotherapie und Chemotherapie (CHOP) bis zu Immuntherapien (IFNa2a, IL2, Rituximab).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001050051136
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  • 8
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    Cutaneous Antimicrobial Defense and Th17-Cell Function in CTCL (2014)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2014-11-01
    Description: Purpose: Primary cutaneous T-cell lymphomas (CTCL) are neoplastic disorders of skin-homing T cells. Affected skin areas show morphologic similarities with alterations in other T-cell–mediated dermatoses. Furthermore, as in atopic dermatitis but in contrast with psoriasis, patients with CTCL are frequently afflicted by cutaneous bacterial infections that support the survival of lymphoma cells. Our aim was to investigate the mechanisms of elevated susceptibility to cutaneous infections in patients with CTCL. Experimental Design: Skin samples from CTCL, psoriasis, and atopic dermatitis patients were used to illuminate the antibacterial competence status and the presence of its modulating cytokines. For substantiation of findings, 3-dimensional epidermis models, isolated and in vitro generated Th-subpopulations, were applied. Parameters were analyzed via qPCR and IHC. Results: CTCL lesions compared with psoriatic lesions presented an impaired upregulation of antibacterial proteins (ABPs), with levels even below those in atopic dermatitis. This was associated with a relative deficiency of the ABP-inducing cytokine IL-17 and a strong presence of the ABP-downregulating cytokine IL-13. The simultaneous presence of the Th17-cell cytokine IL-26 indicated that IL-17 deficiency in CTCL lesions results from functional deviation of Th17 cells. Accordingly, IL-17 but not IL-26 production by Th17 cells in vitro was inhibited by IL-4Rα ligand. Levels of other ABP inducers were comparable between CTCL and psoriasis lesions. The same was true about IL-22/TNF-α targets, including the keratinocyte hyper-regeneration marker K16 and the matrix-degrading enzyme MMP1. Conclusion: Our results suggest that the cutaneous bacterial infections in CTCL are caused by impaired ABP induction as consequence of Th2-mediated biased Th17-cell function. Clin Cancer Res; 20(21); 5507–16. ©2014 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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