Prognostic Biomarkers in Evolving Melanoma Immunotherapy.

Melanoma, a highly aggressive form of skin cancer, has seen significant advancements in treatment through the introduction of immunotherapy. However, the variability in patient responses underscores the need for reliable biomarkers to guide treatment decisions. This article reviews key biomarkers in melanoma immunotherapy, such as PD-L1 expression, tumor mutational burden (TMB), and gene expression profiles (GEPs).

Treatment of a Complex Case of Scleromyxedema Using a Novel Intravenous Immunoglobulin Preparation.

Introduction: We provide a case report on a patient with scleromyxedema treated with high-dose intravenous immunoglobulins (IVIgs) who reported less fatigue and fewer headaches after transitioning to Yimmugo, a novel IVIg preparation. Scleromyxedema is a rare and chronic cutaneous mucinosis, frequently associated with monoclonal gammopathy and systemic complications, which may be life-threatening. The disease is characterized by papular eruptions and sclerosis of the skin.

Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC).

Non-melanoma skin cancer (NMSC) is primarily categorized into basal cell carcinoma (BCC), the most prevalent form of skin cancer, and cutaneous squamous cell carcinoma (cSCC), the second most common type. Both BCC and cSCC represent a significant health burden, particularly in immunocompromised individuals and the elderly. The immune system plays a pivotal role in the development and progression of NMSC, making it a critical focus for therapeutic interventions.

Computerizing the first step of the two-step algorithm in dermoscopy: A convolutional neural network for differentiating melanocytic from non-melanocytic skin lesions.

Importance: Convolutional neural networks (CNN) have shown performance equal to trained dermatologists in differentiating benign from malignant skin lesions. To improve clinicians' management decisions, additional classifications into diagnostic categories might be helpful.

Methods: A convenience sample of 100 pigmented/non-pigmented skin lesions was used for a cross-sectional two-level reader study including 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information).

T Cell-Engaging Bispecific Antibodies Targeting gp100 and PRAME: Expanding Application from Uveal Melanoma to Cutaneous Melanoma.

Uveal melanoma represents a rare and aggressive subtype of melanoma with limited treatment options and poor prognosis, especially in the metastatic setting. Tebentafusp, a bispecific fusion protein, offers a promising therapeutic approach by targeting gp100, an antigen highly expressed in uveal melanoma cells, and redirecting T cell-mediated cytotoxicity towards tumor cells. This review provides an overview of the preclinical and clinical data on tebentafusp in the management of metastatic uveal melanoma.

Tebentafusp Induces a T-Cell-Driven Rash in Melanocyte-Bearing Skin as an Adverse Event Consistent with the Mechanism of Action.

Tebentafusp is a gp100xCD3-bispecific ImmTAC designed to redirect polyclonal T cells against cells presenting the melanocyte lineage-specific antigen gp100 on HLA-A∗02:01. Skin-related adverse events, predominantly rash, are frequent and occur within a few hours after initial infusions; yet, the mechanisms are unknown. In this study, we analyzed clinical data from the randomized phase 3 trial (NCT03070392) of tebentafusp (n = 252) versus investigator's choice (n = 126).

Chemokines and Cytokines in Immunotherapy of Melanoma and Other Tumors: From Biomarkers to Therapeutic Targets.

Chemokines and cytokines represent an emerging field of immunotherapy research. They are responsible for the crosstalk and chemoattraction of immune cells and tumor cells. For instance, CXCL9/10/11 chemoattract effector CD8 T cells to the tumor microenvironment, making an argument for their promising role as biomarkers for a favorable outcome.

Successful Treatment of Severe Pemphigus Vulgaris with Reduced Side Effects Using a Novel IVIg Preparation.

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis (AIBD) characterized by painful blistering of the skin and mucosa caused by autoantibodies that lead to loss of adhesion in the epidermis. Standard therapy for PV is corticosteroids, either alone or in combination with steroid-sparing immunosuppressants or infusions with rituximab. According to the published European guideline, high-dose intravenous immunoglobulin (IVIg) therapy with a dosage of 2 g per kg body weight distributed over 2-5 days every 4 weeks is a promising treatment option, especially for severe or refractory disease.

Performance of an automated total body mapping algorithm to detect melanocytic lesions of clinical relevance.

Importance: Total body photography for skin cancer screening is a well-established tool allowing documentation and follow-up of the entire skin surface. Artificial intelligence-based systems are increasingly applied for automated lesion detection and diagnosis.

Design And Patients: In this prospective observational international multicentre study experienced dermatologists performed skin cancer screenings and identified clinically relevant melanocytic lesions (CRML, requiring biopsy or observation).

Differential Immunoexpression of Inhibitory Immune Checkpoint Molecules and Clinicopathological Correlates in Keratoacanthoma, Primary Cutaneous Squamous Cell Carcinoma and Metastases.

Beyond established anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy, T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) and its ligand CD155 are promising novel inhibitory immune checkpoint targets in human malignancies. Yet, in cutaneous squamous cell carcinoma, evidence on the collective expression patterns of these inhibitory immune checkpoints is scarce. Complete tumour sections of 36 cutaneous squamous cell carcinoma, 5 cutaneous metastases and 9 keratoacanthomas, a highly-differentiated, squamoproliferative tumour, with disparately benign biologic behaviour, were evaluated by immunohistochemistry for expression of programmed cell death ligand 1 (Tumor Proportion Score, Immune Cell Score), TIGIT, CD155 and CD8+ immune infiltrates.

[Primary hyperoxaluria type 1-a rare hereditary metabolic disorder as cause of livedo racemosa].

Livedo racemosa is characterized by a bizarrely configurated lightning figure-like appearance with striated to reticulated, livid erythematous macules and results from a reduced perfusion of the respective skin area, which can have different underlying pathophysiologies. A rare but relevant cause, especially in young patients with end-stage kidney failure, is primary hyperoxaluria type 1 (PH1), a hereditary metabolic disorder in which oxalate accumulates in the body.

A simple tool for evaluation of inflammation in psoriasis: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio as markers in psoriasis patients and related murine models of psoriasis-like skin disease.

Objective parameters to quantify psoriatic inflammation are needed for interdisciplinary patient care, as well as preclinical experimental models. This study evaluates neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in psoriasis patients and five murine models of psoriasis-like skin disease based on topical imiquimod application and overexpression of IL-17A under different promotors. We performed a single-center prospective observational study in a German population, investigating psoriasis patients prior to, 4 weeks, and 16 weeks post begin of systemic anti-inflammatory therapy.

Skin manifestations after immunisation with an adjuvanted recombinant zoster vaccine, Germany, 2020.

BackgroundShortly after the launch of a novel adjuvanted recombinant zoster vaccine (RZV), Shingrix, cases of suspected herpes zoster (HZ) or zoster-like skin reactions following immunisation were reported.AimWe aimed to investigate if these skin manifestations after administration of RZV could be HZ.MethodsBetween April and October 2020, general practitioners (GP) reporting a suspected case of HZ or zoster-like skin manifestation after RZV vaccination to the Paul-Ehrlich-Institut, the German national competent authority, were invited to participate in the study.

Acute low back pain as infusion-related reaction to monoclonal antibodies.

Monoclonal antibodies, such as PD-1 inhibitors, are increasingly used in various cancers. Acute low back pain as infusion-related reaction (IRR) to monoclonal antibodies is poorly described. We report a bicentric series of 10 cases of acute low back pain due to administration of monoclonal antibodies directed against PD-1/PD-L1 for skin cancer treatment in patients treated at University Hospital Heidelberg and University Medical Center Mainz (Germany).

Regulatory T-cell deficiency leads to features of autoimmune liver disease overlap syndrome in scurfy mice.

Introduction: Scurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies such as antinuclear antibodies (ANA).

[Dermato-neuro syndrome-an acute and life-threatening complication of scleromyxedema Arndt-Gottron].

Scleromyxedema Arndt-Gottron is the systemic variant of lichen myxedematosus in which mucin accumulation occurs in the dermis. The disease is usually chronically progressive and extracutaneous manifestations or complications are possible. The pathogenesis is unknown and the disease is usually associated with monoclonal gammopathy.

Lymphatic vessel involvement in primary cutaneous B-cell lymphoma: A common finding?

Background: Cutaneous B-cell lymphoma (CBCL) is part of dermatopathological routine diagnostics. However, in contrast to cutaneous T-cell lymphomas, there are only a few studies on the prevalence and possible clinical impact of lymphatic vessel involvement. Therefore, this pilot study aimed to quantify the prevalence of lymphovascular involvement in CBCL and to assess the association between lymphovascular involvement and recurrence.

Cardiovascular comorbidity in psoriasis - psoriatic inflammation is more than just skin deep.

Background: There is a growing understanding of inflammation in psoriasis beyond its dermatological manifestation, towards systemic inflammation. Management of possible comorbidities encompassing psychological, metabolic and cardiovascular disease is recommended in national and international dermatology guidelines for treatment of psoriasis patients. Vice versa, psoriasis is being recognized as a new risk factor for cardiovascular inflammation within the cardiological community.

Assessment of Diagnostic Performance of Dermatologists Cooperating With a Convolutional Neural Network in a Prospective Clinical Study: Human With Machine.

Importance: Studies suggest that convolutional neural networks (CNNs) perform equally to trained dermatologists in skin lesion classification tasks. Despite the approval of the first neural networks for clinical use, prospective studies demonstrating benefits of human with machine cooperation are lacking.

Objective: To assess whether dermatologists benefit from cooperation with a market-approved CNN in classifying melanocytic lesions.

S100 as Serum Tumor Marker in Advanced Uveal Melanoma.

S100 protein is routinely used as a serum tumor marker in advanced cutaneous melanoma. However, there is scarce and inconclusive evidence on its value in monitoring disease progression of uveal melanoma. In this monocenter study, we retrospectively assessed the connection between documented S100 protein levels of patients suffering from stage IV uveal melanoma and the clinical course of disease.