Basophile Granulozyten sind an allergischen Entzündungen und neuro-immunen Interaktionen bei atopischer Dermatitis (AD) beteiligt. In dieser Arbeit wurde erstmals die Transient receptor potential ankyrin 1-Kanal (TRPA1) -Expression in basophilen Granulozyten von nicht-atopischen Spendern und AD-Patienten untersucht. TRPA1 war in beiden Gruppen nachweisbar, jedoch bei AD signifikant erhöht. Kalziumfluss-Assays bestätigten die Kanalaktivität nach JT010-Stimulation, ohne Effekte auf CD203c- oder CD63-Expression. TRPA1 wurde durch IL-3, IL-31, NGFβ und ein saures Milieu verstärkt, nicht jedoch durch erhöhte Temperatur. Immunfluoreszenz von AD-Läsionen zeigte TRPA1-positive Basophile. Zudem wurde eine durch IL-3, IL-33, NGFβ und pH-Modulation beeinflusste TRPA1/Transient receptor potential vanilloid 1 (TRPV1) -Koexpression festgestellt. Diese Ergebnisse unterstreichen die Rolle basophiler Granulozyten und von TRP-Kanälen in der AD-Pathogenese.
Basophil granulocytes contribute to allergic inflammation and neuro-immune crosstalk in atopic dermatitis (AD). In this study, transient receptor potential ankyrin 1 (TRPA1) expression was investigated in basophils from nonatopic donors and AD patients. TRPA1 was detected in both groups but significantly upregulated in AD. Functional assays confirmed channel activity upon stimulation with the agonist JT010, without changes in CD203c or CD63 expression. TRPA1 levels increased after exposure to IL-3, IL-31, NGFβ, or acidic pH, while temperature had no effect. Immunofluorescence of lesional AD skin confirmed TRPA1-positive basophils. Co-expression with transient receptor potential vanilloid 1 (TRPV1) was shown in basophils and modulated by IL-3, IL-33, NGFβ, and acidic conditions. These findings reveal that basophils express functional TRPA1 and co-express TRPA1/TRPV1, highlighting their potential role in AD pathogenesis.
Deutsche Dermatologische Gesellschaft Journal der Deutschen Dermatologischen Gesellschaft Berlin : Wiley-Blackwell, 2003 23(2025), 12, Seite 1604-1606 Online-Ressource
Introduction - For rare skin cancers, few data exist on the outcome of systemic therapies, particularly immune checkpoint inhibition (ICI). The present study analysed the real-world use of different systemic therapies including ICI, and its outcome in patients with advanced rare skin cancers. - Methods - This retrospective multicenter study included patients who received systemic therapy for advanced, non-resectable cutaneous angiosarcoma (AS), Kaposi sarcoma (KS), pleomorphic dermal sarcoma (PDS), or cutaneous adnexal carcinoma (CAC). Study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). - Results - 209 patients (77 AS; 81 KS; 14 PDS; and 37 CAC) from 30 centers were included. As first-line treatment AS and KS patients predominantly received chemotherapy (77.9%; 63.0%), while PDS and CAC patients mostly received ICI (64.4%; 43.2%). BOR in first-line across all therapy types was 65.5% in KS, 50.0% in PDS, 41.6% in AS, and 10.8% in CAC. BOR for ICI was 66.6% for PDS, 58.3% for AS, 33.3% for KS, and 4.3% for CAC, irrespective of treatment line. 1-year PFS rate upon any first-line therapy was 70.7% for PDS, 45.7% for KS, 25.6% for AS, and 18.5% for CAC (p<0.001). 1-year tumor-specific OS rate was 97.3% in KS, 84.2% in AS, 67.7% in PDS, and 65.4% in CAC (p<0.001). - Conclusions - Type and outcome of systemic therapy differed between cancer entities. Efficacy of ICI was high in PDS and AS, moderate in KS, and low in CAC. Patients with advanced CAC revealed an extremely poor prognosis regardless of the type of therapy used.
European journal of cancer Amsterdam [u.a.] : Elsevier, 1992 228(2025) vom: Okt., Artikel-ID 115750, Seite 1-10
Background - Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis. Preclinical studies indicate a beneficial effect, clinical data has been inconsistent. - Methods - We examined a cohort of advanced, non-resectable melanoma patients (n = 2419) derived from the German prospective multicenter skin cancer registry ADOReg, who were treated with immune checkpoint inhibitors (ICI). The patients were classified based on whether it was documented that they received platelet aggregation inhibition (PAI) (n = 137) (acetylsalicylic acid (ASA) or clopidogrel), anticoagulation (AC) (n = 185) (direct oral anticoagulation (DOAC), phenprocoumon, heparins) at the start of ICI or no antithrombotic medication (n = 2097) at any point during ICI treatment. The study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). - Results - A significantly improved PFS was observed in patients documented to receive ASA (15.1 vs 6.4 months, HR 0.67, 95 % CI: 0.5 to 0.88, p = 0.0047) as well as in patients to receive AC (15.1 vs. 6.4 months, HR 0.7, 95 % CI: 0.53 to 0.91, p = 0.01) compared to patients for whom no antithrombotic medication was documented. Multivariate analysis of OS showed significant risk reduction in patients who received DOAC (HR 0.68, 95 % CI: 0.49 to 0.92, p = 0.0170) or phenprocoumon (HR: 0.44, 95 % CI: 0.19 to 0.85, p = 0.0301). - Conclusion - Our study indicates a positive prognostic effect of anticoagulant and antiplatelet concomitant medication in melanoma patients receiving ICI. Further studies are needed to confrim the cancer-related benefit of adding anticoagulation or platelet inhibition to ICI treatment.
European journal of cancer Amsterdam [u.a.] : Elsevier, 1992 214(2025) vom: Jan., Artikel-ID 115159, Seite 1-11
