Cutaneous T-cell lymphomas

Samuelson, Ellen

doi:10.1016/s0749-2081(98)80007-7

Cited by 9 publications

(12 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…42 Skin samples from 5 patients with a confirmed diagnosis of CTCL were analyzed; NS and AD skin were used as controls. The following combinations of primary antibodies were used: (1) anti-CD4 (Abcam), -TOX (Sigma); (2) For pSTAT-6 determination, freshly isolated CD4 1 T cells from SS patients or NDs were incubated for 15 minutes with IL-4 (10 ng/mL), IL-13 (30 ng/mL), or medium alone at 37°C. Cells were permeabilized in ice-cold 90% methanol and then stained with an anti-pSTAT-6 mAb (Cell Signaling).…”

Section: Immunohistochemistry and Confocal Microscopymentioning

confidence: 99%

Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation

Geskin¹,

Viragova²,

Stolz

et al. 2015

Blood

135

113

View full text Add to dashboard Cite

Key Points• IL-13 is an autocrine factor for CTCL.• IL-13 and its receptors represent novel markers of CTCL malignancy and potential therapeutic targets for intervention.Cutaneous T-cell lymphomas (CTCLs) primarily affect skin and are characterized by proliferation of mature CD4 1 T-helper cells. The pattern of cytokine production in the skin and blood is considered to be of major importance for the pathogenesis of CTCLs. Abnormal cytokine expression in CTCLs may be responsible for enhanced proliferation of the malignant cells and/or depression of the antitumor immune response. Here we show that interleukin-13 (IL-13) and its receptors IL-13Ra1 and IL-13Ra2 are highly expressed in the clinically involved skin of CTCL patients. We also show that malignant lymphoma cells, identified by the coexpression of CD4 and TOX (thymus high-mobility group box), in the skin and blood of CTCL patients produce IL-13 and express both receptors. IL-13 induces CTCL cell growth in vitro and signaling through the IL-13Ra1. Furthermore, antibody-mediated neutralization of IL-13 or soluble IL-13Ra2 molecules can lead to inhibition of tumor-cell proliferation, implicating IL-13 as an autocrine factor in CTCL. Importantly, we established that IL-13 synergizes with IL-4 in inhibiting CTCL cell growth and that blocking the IL-4/IL-13 signaling pathway completely reverses tumor-cell proliferation. We conclude that IL-13 and its signaling mediators are novel markers of CTCL malignancy and potential therapeutic targets for intervention. (Blood. 2015;125(18):2798-2805

show abstract

Section: Immunohistochemistry and Confocal Microscopymentioning

confidence: 99%

Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation

Geskin¹,

Viragova²,

Stolz

et al. 2015

Blood

135

113

View full text Add to dashboard Cite

show abstract

“…The course of MF is usually indolent and will progress over years, but the prognosis is drastically worsened with the development of tumors and disease dissemination extracutaneously to lymph nodes and other organs. [1][2][3] Cytokines bind specific cell surface receptors and activate intracellular signal transduction pathways, often involving the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The JAK proteins comprise a family of nonreceptor tyrosine kinases that are constitutively associated with cytoplasmic membrane-proximal regions of various receptors.…”

Section: Introductionmentioning

confidence: 99%

In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3

et al. 2004

View full text Add to dashboard Cite

A characteristic feature of neoplastic transformation is a perpetual activation of oncogenic proteins. Here, we studied signal transducers and activators of transcription (STAT) in patients with mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL). Malignant lymphocytes in dermal infiltrates of CTCL tumors showed frequent and intense nuclear staining with anti-PY-STAT3 antibody, indicating a constitutive activation of STAT3 in vivo in tumor stages. In contrast, only sporadic and faint staining was observed in indolent lesions of patch and plaque stages of MF. Moreover, neoplastic lymphocytes in the epidermal Pautrier abscesses associated with early stages of MF did not express activated STAT3. To address the role of STAT3 in survival/apoptosis, CTCL tumor cells from an advanced skin tumor were transfected with either wild-type STAT3 (STAT3wt) or dominant-negative STAT3 (STAT3D). Forced inducible expression of STAT3D triggered a significant increase in tumor cells undergoing apoptosis, whereas forced expression of STAT3wt or empty vector had no effect. In conclusion, a profound in vivo activation of STAT3 is observed in MF tumors but not in the early stages of MF. Moreover, STAT3 protects tumor cells from apoptosis in vitro. Taken together, these findings suggest that STAT3 is a malignancy factor in CTCL.

show abstract

“…Cutanous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphomas, of which mycosis fungoides (MF) and the leukemic variant Sézary syndrome (SS) are the most common (reviewed in Samuelson, 1 Diamandidou et al 2 ). Although viral transformation with human T-cell lymphotropic virus type 1 has been found in some cases of CTCL, 3 it does not seem to be the agent causing MF.…”

Section: Introductionmentioning

confidence: 99%

“…In SS, the leukemic form of MF, tumor T cells are present both in the skin and in the blood. 1 Previously, several groups have investigated cytokine production in skin lesions or peripheral blood from CTCL patients to establish whether a unique cytokine profile could be associated with the disease. Although the results of these studies have not been entirely concordant, the general concept is that a shift in cytokine profile from T H 1 to T H 2 accompanies disease progression.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous interleukin-5 production in cutaneous T-cell lymphoma lines is mediated by constitutively activated Stat3

Nielsen

Nissen

Gerwien

et al. 2002

Blood

View full text Add to dashboard Cite

Mycosis fungoides is a low-grade cutanous T-cell lymphoma (CTCL) of unknown etiology. In advanced stages of CTCL, a shift in cytokine profile from T H 1 to T H 2 is observed, which coincides with eosinophilia, high levels of immunoglobulin E, and increased susceptibility to bacterial infections. It is, however, unknown why T H 2 cytokines predominate in advanced CTCL, and the cellular source of these cytokines also remains to be identified. In several leukemias and lymphomas, constitutively activated signal transducer and activator of transcription (Stat) signaling pathways have been detected. In a previous study, constitutive activation of Stat3 was found in tumor cells isolated from affected skin and blood from CTCL patients. Here, it is shown that CTCL tumor cell lines, but not nonmalignant cell lines, spontaneously produce interleukin-5 (IL-5), IL-6, and IL-13. Transfection of tumor cells with dominantnegative Stat3 almost completely blocks IL-5 production and strongly inhibits IL-13 production, whereas IL-6 production is unaffected. Thus, the data show that malignant CTCL cells themselves might contribute to the change in cytokine pattern accompanying progression of CTCL. In conclusion, constitutively activated Stat3 is found to mediate a spontaneous IL-5 production and regulate IL-13 production in CTCL cell lines, pointing toward a new role of Stat3 in malignant transformation. (Blood. 2002;99:973-977)

show abstract

Cutaneous T-cell lymphomas

Cited by 9 publications

References 44 publications

Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation

Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation

In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3

Spontaneous interleukin-5 production in cutaneous T-cell lymphoma lines is mediated by constitutively activated Stat3

Contact Info

Product

Resources

About