Antibiotics inhibit tumor and disease activity in cutaneous T-cell lymphoma

Lindahl, Lise M.; Willerslev-Olsen, Andreas; Gjerdrum, Lise Mette Rahbek; Nielsen, Pia Rude; Blümel, Edda; Rittig, Anne Hald; Celis, Pamela; Herpers, Bjorn L.; Becker, Jürgen C.; Stausbøl-Grøn, Brian; Wasik, Mariusz A.; Gluud, Maria; Fredholm, Simon; Buus, Terkild Brink; Johansen, Claus; Nastasi, Claudia; Peiffer, Lukas; Kubat, Linda; Bzorek, Michael; Eriksen, Jens Ole; Krejsgaard, Thorbjørn; Bonefeld, Charlotte M.; Geisler, Carsten; Mustelin, Tomas; Langhoff, Erik; Givskov, Michael; Woetmann, Anders; Kilian, Mogens; Litman, Thomas; Iversen, Lars; Ødum, Niels

doi:10.1182/blood.2018888107

Cited by 100 publications

(100 citation statements)

References 37 publications

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“…It would be worth examining whether expression of other CE proteins is also downregulated by Th2 cytokines. Furthermore, the hypothesis of CTCL pathogenesis, concerning chronic antigen stimulation with bacterial superantigens such as S. aureus leading to the development and clonal proliferation of malignant T-cells seems to be up to date [4,[26][27][28][29]. In the resent study, Lindahl and coworkers reported inhibition of malignant T-cells and clinical improvement in patients with advanced-stage CTCL after antibiotic treatment [29].…”

Section: Discussionmentioning

confidence: 99%

Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

et al. 2020

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The skin barrier defect in cutaneous T-cell lymphomas (CTCL) was recently confirmed to be similar to the one observed in atopic dermatitis (AD). We have examined the expression level of cornified envelope (CE) proteins in CTCL, AD and healthy skin, to search for the differences and their relation to the courses of both diseases. The levels of FLG, FLG2, RPTN, HRNR, SPRR1A, SPRR1B, SPRR3 and LELP-1 mRNA were determined by qRT-PCR, while protein levels were examined using the ELISA method in skin samples. We have found that mRNA levels of FLG, FLG2, LOR, CRNN and SPRR3v1 were decreased (p ≤ 0.04), whereas mRNA levels of RPTN, HRNR and SPRR1Av1 were increased in lesional and nonlesional AD skin compared to the healthy control group (p ≤ 0.04). The levels of FLG, FLG2, CRNN, SPRR3v1 mRNA increased (p ≤ 0.02) and RPTN, HRNR and SPRR1Av1 mRNA decreased (p ≤ 0.005) in CTCL skin compared to the lesional AD skin. There was a strong correlation between the stage of CTCL and increased SPRR1Av1 gene expression at both mRNA (R = 0.89; p ≤ 0.05) and protein levels (R = 0.94; p ≤ 0.05). FLG, FLG2, RPTN, HRNR and SPRR1A seem to play a key role in skin barrier dysfunction in CTCL and could be considered a biomarker for differential diagnosis of AD and CTCL. SPRR1Av1 transcript levels seem to be a possible marker of CTCL stage, however, further studies on a larger study group are needed to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

et al. 2020

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“…[25] Current studies indicate that colonized SSAg-producing S. aureus intensify cutaneous inflammation of atopic dermatitis and Sézary syndrome and promote tumor progression in Sézary syndrome. [26,27] Antibiotics have an ameliorating effect on inflammation in these conditions, [28] [29] Oral antibiotics are also administered as a treatment for LyP. However, because LyP is a chronic condition characterized by intermittent flare ups of lesions, it is difficult to determine the long term effectiveness of anti-Staphylococcal antibiotics for LyP.…”

Section: Discussionmentioning

confidence: 99%

Evidence linking atopy and staphylococcal superantigens to the pathogenesis of lymphomatoid papulosis, a recurrent CD30+ cutaneous lymphoproliferative disorder

2020

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BackgroundPrimary cutaneous CD30+ lymphoproliferative disorders (CD30CLPD) are the second most common type of cutaneous T cell lymphoma (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Case reports and small patient series suggest an association of CD30CLPD with atopic disorders. However, the prevalence of atopy in patients with CD30CLPD in retrospective studies depends on patients' recall which is not always reliable. More objective criteria of atopy include evidence of skin reactivity to allergens (positive prick test) and evidence of allergen-specific IgE in serum. This study was undertaken to test the hypothesis that atopy is prevalent in patients with CD30CLPD using serologic criteria of allergen-specific IgE antibodies to aeroallergens and Staphylococcal aureus enterotoxin superantigens (SSAgs). MethodsWe tested serum samples of CD30CLPD for common IgE-specific airborne allergens with the Phadiatop test, which if positive, is regarded as serologic evidence of atopy in adults. Sera were also tested for IgE antibodies reactive to three Staphylococcal enterotoxins with superantigenic properties (SSAg-IgE). Control sera were obtained from adult subjects evaluated for rhino-sinusitis and a negative Phadiatop test. Patients' history of an atopic disorder was obtained by retrospective chart review.

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“…A recent study further demonstrated that patients exhibiting clinical improvement after transient antibiotic therapy, display diminished STAT3 signaling, IL-2Rα expression and cell proliferation in the lesional skin (Lindahl et al, 2019). Antibiotic treatment not only reduced the disease activity at the clinical and histological level but also resulted in a significant decrease in the fraction of malignant T cells in the lesional skin in the majority of patients (Lindahl et al, 2019). These findings indicate that there may be a mutual sustenance between the malignant T cells and toxin-producing S. aureus where the former compromise the local immunity and the bacteria, in turn, mitigate anti-tumor responses while concurrently fueling the expansion of malignant T cells.…”

Section: Interactions Between Bacterial Toxins and Malignant T Cellsmentioning

confidence: 95%

Cellular Interactions and Inflammation in the Pathogenesis of Cutaneous T-Cell Lymphoma

Stolearenco

Namini

Hasselager

et al. 2020

Front. Cell Dev. Biol.

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Cutaneous T-cell lymphoma (CTCL) comprises a group of lymphoproliferative diseases characterized by the accumulation of malignant T cells in chronically inflamed skin lesions. In early stages, the disease presents as skin patches or plaques covering a limited area of the skin and normally follows an indolent course. However, in a subset of patients the cutaneous lesions develop into tumors and the malignant T cells may spread to the lymphatic system, blood and internal organs with fatal consequences. Despite intensive research, the mechanisms driving disease progression remain incompletely understood. While most studies have focused on cancer cell-intrinsic oncogenesis, such as genetic and epigenetic events driving malignant transformation and disease progression, an increasing body of evidence shows that the interplay between malignant T cells and non-malignant cells plays a crucial role. Here, we outline some of the emerging mechanisms by which tumor, stromal and epidermal interactions may contribute to the progression of CTCL with particular emphasis on the crosstalk between fibroblasts, keratinocytes and malignant T cells.

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Antibiotics inhibit tumor and disease activity in cutaneous T-cell lymphoma

Abstract: This paper reports that aggressive antibiotic treatment inhibits disease activity and lymphocyte proliferation in cutaneous T-cell lymphoma (CTCL). The study offers important evidence for a link between bacterial infection, activation of the immune system, and CTCL progression.

Cited by 100 publications

References 37 publications

Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

Evidence linking atopy and staphylococcal superantigens to the pathogenesis of lymphomatoid papulosis, a recurrent CD30+ cutaneous lymphoproliferative disorder

Cellular Interactions and Inflammation in the Pathogenesis of Cutaneous T-Cell Lymphoma

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