Investigating heredity in cutaneous T-cell lymphoma in a unique cohort of Danish twins

Ødum, Niels; Lindahl, Lise M.; Wod, Mette; Krejsgaard, Thorbjørn; Skytthe, Axel; Woetmann, Anders; Iversen, Lars; Christensen, Kaare

doi:10.1038/bcj.2016.128

Cited by 27 publications

(26 citation statements)

References 12 publications

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“…Mycosis fungoides (MF) is the most prevalent form and Sézary syndrome (SS) is an aggressive leukemic variant of the disease. 1 CTCL patients have an increased risk of contracting severe infections compared to healthy controls, 2,3 which constitute a major cause of death. 4 The most frequently found pathogen is Staphylococcus aureus (S. aureus), infecting 44-76% of CTCL patients.…”

Section: Introductionmentioning

confidence: 99%

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4⁺ T cells in cutaneous T-cell lymphoma

et al. 2019

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Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4 + T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4 + T cells increases significantly following exposure to alphatoxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4 + T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4 + T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4 + T cells, identifying alpha-toxin as a putative drug target in CTCL.

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Section: Introductionmentioning

confidence: 99%

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4⁺ T cells in cutaneous T-cell lymphoma

et al. 2019

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“…However, it has become clear that colonization with SE-producing S. aureus may also drive deregulation of signal transducers and activators of transcription (STAT), cytokine release, and/or disease progression of chronic skin diseases such as atopic dermatitis and cutaneous T cell lymphoma [ 26 – 30 ]. Interestingly, clinically infections with S. aureus and other bacteria generally occur after diagnosis [ 31 ], i.e. after skin lesions with compromised skin barriers have become evident supporting the notion that SE producing bacteria may aggravate CTCL without necessarily playing a primary etiological role triggering the disease in the first place [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, clinically infections with S. aureus and other bacteria generally occur after diagnosis [ 31 ], i.e. after skin lesions with compromised skin barriers have become evident supporting the notion that SE producing bacteria may aggravate CTCL without necessarily playing a primary etiological role triggering the disease in the first place [ 31 ]. As IL-26 expression is greatly enhanced in CTCL lesions [ 32 ], it may be speculated that an increased expression of IL-26 in situ reflects an increased burden of SE-producing S. aureus in CTCL skin lesions as previously reported by Jackow et al [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Interleukin-26 (IL-26) is a novel anti-microbial peptide produced by T cells in response to staphylococcal enterotoxin

et al. 2018

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Anti-microbial peptides are produced at outer and inner surfaces by epithelia and innate immune cells in response to bacterial infection. Staphylococcus aureus is an enterotoxin producing, Gram-positive pathogen, which is a major cause of soft tissue infections and life-threatening bacteremia and sepsis. Here we show that (i) skin T cells in chronic wounds infected with S. aureus express interleukin-26 (IL-26) in situ, (ii) staphylococcal enterotoxins (SE) trigger IL-26 expression in T cell lines and primary skin T cells, and (iii) IL-26 triggers death and inhibits biofilm formation and growth of S. aureus. Thus, we provide novel evidence that IL-26 is an anti-microbial peptide produced by T cells in response to SE. Accordingly, we propose that IL-26 producing T cells take part in the innate immune response to SE producing S. aureus and thus play a novel role in the primary innate immune defense in addition to their classical role in adaptive immunity.

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“…A comprehensive study, taking advantage of the Danish cohort of twins, suggested that CTCL has very few heritable components, and several lines of evidence indicate that environmental factors may play a promoting or even initiating role in the carcinogenesis of CTCL [5,45]. Accordingly, it may be speculated that exogeneous factors including drugs, pesticides, and bacterial toxins may promote disease progression [5].…”

Section: Dysregulation Of Mirs In Ctclmentioning

confidence: 99%

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas

Gluud

Willerslev-Olsen

Gjerdrum

et al. 2020

Cancers

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Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.

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Investigating heredity in cutaneous T-cell lymphoma in a unique cohort of Danish twins

Cited by 27 publications

References 12 publications

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4⁺ T cells in cutaneous T-cell lymphoma

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4⁺ T cells in cutaneous T-cell lymphoma

Interleukin-26 (IL-26) is a novel anti-microbial peptide produced by T cells in response to staphylococcal enterotoxin

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas

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Investigating heredity in cutaneous T-cell lymphoma in a unique cohort of Danish twins

Cited by 27 publications

References 12 publications

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma

Interleukin-26 (IL-26) is a novel anti-microbial peptide produced by T cells in response to staphylococcal enterotoxin

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas

Contact Info

Product

Resources

About

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4⁺ T cells in cutaneous T-cell lymphoma

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4⁺ T cells in cutaneous T-cell lymphoma