BCCs following radiation therapy for tinea capitis show unique histological characteristics related to aggressive behaviour. These aggressive features did not reflect the clinical behaviour in the current cohort.
Background: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease. Most patients require long-term therapy with systemic steroids, and a steroid-sparing agent is usually also utilized. Dapsone is a chemotherapeutic agent with anti-inflammatory properties that is used as a steroid-sparing agent in PV. Objective: The aim of the present study was to evaluate the efficacy of dapsone as an adjuvant therapy in patients with PV. Methods: A retrospective analysis of patients' files was performed. All 26 patients included in the study group were treated with dapsone as an adjuvant to systemic steroids for at least 3 consecutive months and were followed up during their dapsone treatment period. Results: After 3 months of treatment with dapsone, 13 patients were in the consolidation phase, 4 patients demonstrated partial remission on minimal therapy, 7 patients demonstrated complete remission on minimal therapy, and 2 patients were defined as treatment failures. The trend of clinical improvement continued after 6 months of treatment and at the study end point. Conclusion: This retrospective case series, one of the largest reported, indicates that dapsone is efficacious and safe for patients with PV in whom it is well tolerated soon after the initiation of treatment.
The effect of tumor/T-cell interactions on subsequent immune infiltration is undefined. Here we report that pre-exposure of melanoma cells to cognate T cells enhanced the chemotaxis of new T cells in vitro. The effect was HLA class I–restricted and IFNγ-dependent, as it was abolished by β2M-knockdown, MHC-blocking antibodies, JAK1 inhibitors, JAK1-silencing and IFNgR1-blocking antibodies. RNA-sequencing of 73 melanoma metastases showed a significant correlation between the interferon-inducible p150 isoform of adenosine-deaminase-acting-on-RNA-1 (ADAR1) enzyme and immune infiltration. Consistent with this, co-cultures of cognate melanoma/T-cell pairs led to IFNγ-dependent induction of ADAR1-p150 in the melanoma cells, as visualized in situ using dynamic cell blocks, in ovo using fertilized chick eggs, and in vitro with Western blots. ADAR1 staining and RNA-sequencing in patient-derived biopsies following immunotherapy showed a rise in ADAR1-p150 expression concurrently with CD8+ cell infiltration and clinical response. Silencing ADAR1-p150 abolished the IFNγ-driven enhanced T-cell migration, confirming its mechanistic role. Silencing and overexpression of the constitutive isoform of ADAR1, ADAR1-p110, decreased and increased T-cell migration, respectively. Chemokine arrays showed that ADAR1 controls the secretion of multiple chemokines from melanoma cells, probably through microRNA-mediated regulation. Chemokine receptor blockade eliminated the IFNγ-driven T-cell chemotaxis. We propose that the constitutive ADAR1 downregulation observed in melanoma contributes to immune exclusion, whereas antigen-specific T cells induce ADAR1-p150 by releasing IFNγ, which can drive T-cell infiltration.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.