Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study.

Background: Adjuvant immune checkpoint inhibition (ICI) with anti-PD-1 antibodies in high-risk resected melanoma has been shown to improve recurrence-free survival. It is unclear whether prior adjuvant anti-PD-1 therapy is associated with altered response to subsequent ICI treatment in the metastatic setting.

Methods: Using data from the European Melanoma Registry (EUMelaReg), we analyzed the efficiency of first-line (1L) ICI in non-resectable or metastatic melanoma after failure from prior adjuvant anti-PD-1 treatment.

Bilateral In Vivo Confocal Microscopic Changes of the Corneal Subbasal Nerve Plexus in Patients with Acute Herpes Zoster Ophthalmicus.

Introduction: Unilateral herpes zoster ophthalmicus (HZO) results in bilateral corneal denervation in patients with corneal involvement, which correlates with corneal sensation loss. The study aimed to analyze bilateral corneal nerve changes in patients with acute unilateral HZO and no keratitis compared with healthy controls.

Methods: This was a prospective, single-center study.

Treatment at the end of life in patients with advanced melanoma. A multicenter DeCOG study of 1067 patients from the prospective skin cancer registry ADOReg.

Background: Although systemic therapies have improved considerably over the last decade, up to 50% of patients with metastatic melanoma still die due to disease progression. Oncological treatment at the end-of-life phase is challenging. The aim of this study was to investigate the frequency and type of systemic therapy received by melanoma patients in their end-of-life phase.

Presence of brain metastasis differentially impacts long-term survival after first-line therapy in melanoma depending on BRAF mutation status.

Background: Modern therapeutic strategies have significantly improved the prognosis of advanced melanoma patients. Predictive factors of therapy response include serum LDH; however, predictive markers for long-term survival are currently largely lacking.

Patients And Methods: Patients diagnosed with stage IV melanoma (AJCCv8) of cutaneous origin or unknown primary were identified from the prospective multicenter German Dermatologic Cooperative Oncology Group (DeCOG) skin cancer registry ADOREG.

Histamine and TH2 cytokines regulate the biosynthesis of cysteinyl-leukotrienes and expression of their receptors in human mast cells.

Introduction: In skin lesions of atopic dermatitis (AD), a chronic inflammatory skin disease, mast cells beyond other immune cells are present in increasing numbers. Upon activation, mast cells release a plethora of mediators, in particular histamine and leukotrienes, as well as chemokines and cytokines, which modulate the immune response of cells in their microenvironment and may influence mast cells in an autocrine loop. This study investigated the effects of histamine and TH2 cytokines on the biosynthesis of cysteinyl leukotrienes (CysLTs) as well as CysLT receptor expression on human mast cells from healthy volunteers and patients with AD.

Characterization of Hospital Admissions During Immune Checkpoint Inhibitor Therapy: Insights From the ICOG Study.

Introduction: Immune checkpoint inhibitors (ICI) have improved the therapeutic arsenal in outpatient oncology care; however, data on necessity of hospitalizations associated with immune-related adverse events (irAEs) are scarce. Here, we characterized hospitalizations of patients undergoing ICI, from the prospective cohort study of the immune cooperative oncology group (ICOG) Hannover.

Methods: Between 12/2019 and 06/2022, 237 patients were included.

A comparison of real-world data on adjuvant treatment in patients with stage III BRAF V600 mutated melanoma - Results of systematic literature research.

Background: Over the past decade, PD-1-based immune checkpoint inhibitors (ICI) and targeted therapies (TT) with BRAF and MEK inhibitors transformed melanoma treatment. Both are widely used in the adjuvant setting. However, for patients with a BRAF V600 mutation, the optimal adjuvant therapy remains unclear due to the lack of head-to-head comparison studies.

Improved survival of advanced melanoma patients receiving immunotherapy with concomitant antithrombotic therapy - A multicenter study on 2419 patients from the prospective skin cancer registry ADOReg.

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.

Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma.

Background: Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study.

Methods: NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504).

Nanopore Sequencing for T-Cell Receptor Rearrangement Analysis in Cutaneous T-Cell Lymphoma.

Analysis of T-cell receptor (TCR) clonality is a major diagnostic tool for lymphomas, particularly for cutaneous T-cell lymphomas (CTCL) like Mycosis fungoides and Sézary syndrome. However, a fast and cost-effective workflow is needed to enable widespread use of this method. : We established a procedure for TCR rearrangement analysis via Oxford Nanopore Technology (ONT) sequencing.

Histamine and Th2 cytokines independently and synergistically upregulate MMP12 expression in human M2 macrophages.

Beyond Th2 cells and various immune cells, M2 macrophages have been identified in lesional skin of atopic dermatitis (AD) indicating their involvement in the disease's underlying mechanisms. MMP12, a matrix-degrading enzyme, which is predominantly produced by macrophages, is increased in skin lesions of AD patients. In this study we investigated the expression of MMP12 mRNA in lesional AD skin at single cell level through RNA sequencing (scRNA-seq) and the expression of MMP12 in M2 macrophages from healthy individuals and AD patients in response to Th2 cytokines and histamine using quantitative PCR and ELISA.

The Prevalence of Sarcopenia in Patients with Solid Tumors Differs Across Regions: A Systematic Review.

The purpose of the meta-analysis was to compare the prevalence of sarcopenia on staging computed tomography (CT) in patients with solid tumors in different world regions. MEDLINE, Embase, and SCOPUS literature databases were screened for prevalence of sarcopenia in oncologic patients up to December 2022. Two hundred eighty studies met the inclusion criteria.

A targetable type III immune response with increase of IL-17A expressing CD4 T cells is associated with immunotherapy-induced toxicity in melanoma.

Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures. This was in line with the finding of an increase in the proportion of CD4 T cells with IL-17A expression at the adverse event onset in the peripheral blood using flow cytometry.

Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- ("Triple") wild type melanomas.

Background: Melanomas lacking mutations in BRAF, NRAS and NF1 are frequently referred to as "triple wild-type" (tWT) melanomas. They constitute 5-10 % of all melanomas and remain poorly characterized regarding clinical characteristics and response to therapy. This study investigates the largest multicenter collection of tWT-melanomas to date.

Influence of adjuvant therapies on organ-specific recurrence of cutaneous melanoma: A multicenter study on 1383 patients of the prospective DeCOG registry ADOReg.

This study investigated whether adjuvant treatments in stage III cutaneous melanoma (CM) influenced patterns of recurrence. Patients with primary (n = 1033) or relapsed CM (n = 350) who received adjuvant therapies with Nivolumab (N), Pembrolizumab (P), or Dabrafenib and Trametinib (D + T) were extracted from the prospective multicenter real-world skin cancer registry ADOReg. Endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), organ-specific DMFS, and overall survival (OS).

Stringent monitoring can decrease mortality of immune checkpoint inhibitor induced cardiotoxicity.

Background: Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed.

The stimulation of TH2 cells results in increased IL-5 and IL-13 production via the H receptor.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting in decreased quality of life. Histamine and specifically the H receptor play a key role in the inflammatory process in AD and serve as targets for novel therapeutic approaches.

Objective: In the present study we aimed to elucidate the immunopathological mechanisms with which the H receptor impacts TH2 cells and contributes to AD pathophysiology.

Anti-tumor effects of tirbanibulin in squamous cell carcinoma cells are mediated via disruption of tubulin-polymerization.

Topical tirbanibulin is a highly effective and well tolerated novel treatment option for actinic keratoses (AKs). This study aimed to characterize the mode of action of tirbanibulin in keratinocytes (NHEK) and cutaneous squamous cell carcinoma (cSCC) cell lines (A431, SCC-12) in vitro. Tirbanibulin significantly reduced proliferation in a dose-dependent manner in all investigated cell lines, inhibited migration, and induced G2/M-cell cycle arrest only in the cSCC cell lines analyzed, and induced apoptosis solely in A431, which showed the highest sensitivity to tirbanibulin.