Dendritic cell (DC) activation by pattern recognition receptors like Toll-like-receptors (TLRs) is crucial for cancer immunotherapies. Here, we demonstrate the effectiveness of the TLR7/8 agonist imiquimod (IMQ) in treating both local tumors and distant metastases. Administered orally, IMQ activates plasmacytoid DCs (pDCs) to produce systemic type I interferons (IFN-I) required for TLR7/8 upregulation in DCs and macrophages, sensitizing them to topical IMQ treatment, which is essential for therapeutic efficacy.
View Article and Find Full Text PDFThe hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signaling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche.
View Article and Find Full Text PDFFinding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.
View Article and Find Full Text PDFFinding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA () that is upregulated in NRAS/MAPK-dependent melanoma, and that we named .
View Article and Find Full Text PDFBackground And Objectives: This study analyzed the extent to which the recent introduction of more effective treatments has led to an improvement in real-world psoriasis patients.
Patients And Methods: Patient characteristics and the first-year treatment effectiveness in biologic-naive patients have been analyzed since 2004 until now, irrespective of treatment switches.
Results: Data from 2,729 patients were eligible for this analysis.
Background: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans.
View Article and Find Full Text PDFBackground: Apremilast, an oral phosphodiesterase 4 inhibitor, is approved in the European Union for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients refractory or contraindicated to or intolerant of other systemic therapies.
Objectives: The APPRECIATE study assessed apremilast use in real-world practice and its clinical value to physicians and patients. APPRECIATE was a multinational, observational, retrospective, cross-sectional study.
Immunosuppressive therapy is standard for the treatment of inflammatory diseases and for minimizing rejection in transplant patients. However, immunosuppressant drugs are associated with an increased risk of certain cancers. In particular, melanoma is an immunogenic tumor and as such, is strongly influenced by the immune system.
View Article and Find Full Text PDFBackground: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions.
View Article and Find Full Text PDFIntroduction: We investigated whether governmental measures and lockdowns during the COVID-19 pandemic had an impact on the number and histopathologic stages of melanoma.
Methods: The number and thickness (Breslow) of all diagnosed melanomas per day, month, or period at the 'Institute for Pathology in the Centre' in 2019 and 2020 were compared. For 2020, we defined four time periods: Period 1: 1 January-15 March; Period 2: 16 March-15 May (Lockdown 1); Period 3: 16 May-2 November; Period 4: 3 November-7 December (Lockdown 2).
Topical cyclosporine (CSA) has been reported as an alternative treatment in steroid-refractory oral lichen planus (OLP), but evidence is limited and conflicting. An N-of-1 trial setting could be appropriate to evaluate interindividual differences in treatment response. We studied a series of 21 open-label, biphasic single-patient observations.
View Article and Find Full Text PDFBackground: Little is known about the effectiveness and drug survival associated with apremilast under real-world conditions.
Objective: To investigate the influence of patient and disease characteristics on drug survival associated with apremilast and to elucidate clinical effectiveness with regard to the psoriasis area and severity index (PASI) reduction.
Methods: This was an observational, retrospective, multicenter analysis from the Austrian Psoriasis Registry.
Background And Objectives: It has been postulated that psoriasis is associated with tongue lesions and geographic tongue might be "oral psoriasis". However, reports are inconclusive, prevalence rates vary and data for Europe are sparse. In this prospective case-control study we investigated the point-prevalence of tongue conditions in an Austrian cohort.
View Article and Find Full Text PDFBackground: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options.
Objectives: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment.
J Eur Acad Dermatol Venereol
July 2020
Background: Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease mainly affecting elderly patients. Among several published risk factors, a recent post hoc analysis linked anti-BP180 autoantibodies (AABs) to fatal outcomes in BP. To date, this finding has not been confirmed independently.
View Article and Find Full Text PDFEpidermal growth factor receptor (EGFR)-targeted anticancer therapy induces stigmatizing skin toxicities affecting patients' quality of life and therapy adherence. The lack of mechanistic details underlying these adverse events hampers their management. We found that EGFR/ERK signaling is required in LRIG1-positive stem cells during de novo hair eruption to secure barrier integrity and prevent the invasion of commensal microbiota and inflammatory skin disease.
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