Melanoma

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43-0·74], p<0·0001) compared with placebo, leading to its approval in the USA and Europe. This report provides the final results for the secondary efficacy endpoint, distant metastasis-free survival and an update of the recurrence-free survival results...

No abstract text is available yet for this article.

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and temporal dynamics of the transcription factor TCF1. TCF1 promotes immature NK cell expansion and restrains differentiation...

Metastasis of melanoma significantly worsens prognosis; thus, therapeutic interventions that prevent metastasis could improve patient outcomes. Here, we show using humanized mice that colonization of distant visceral organs with melanoma is dependent upon a human CD33+CD11b+CD117+ progenitor cell subset comprising <4% of the human CD45+ leukocytes. Metastatic tumor-infiltrating CD33+ cells from patients and humanized (h)NSG-SGM3 mice showed converging transcriptional profiles. Single-cell RNA-seq analysis identified a gene signature of a KIT/CD117-expressing CD33+ subset that correlated with decreased overall survival in a TCGA melanoma cohort...

BACKGROUND: Management of patients with sentinel lymph node (SLN)-positive melanoma has changed dramatically over the last few years such that completion lymph node dissection (CLND) has become uncommon, and many patients receive adjuvant immunotherapy or targeted therapy. This study seeks to characterize patterns and predictors of early recurrence in this setting. PATIENTS AND METHODS: All patients with primary cutaneous melanoma undergoing sentinel lymph node biopsy (SLNB) between 3/2016 and 12/2019 were identified...

PURPOSE: Acral lentiginous melanoma (ALM), a relatively rare subtype of cutaneous melanoma, has been reported to have a worse prognosis than other melanomas. We aimed to assess clinical findings in Caucasian ALM patients and compare the data with a matched cohort of superficial spreading melanoma (SSM) patients. METHODS: We studied 63 patients with ALM and 63 randomly stage- and limb-matched patients with SSM (non-ALM). In both cohorts, guideline-adjusted diagnosis, treatment and follow-up were performed...

Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths, and its therapy remains a challenge. Our proposed therapeutic approach is based on the intratumoral injections of mannan-BAM, toll-like receptor ligands, and anti-CD40 antibody (thus termed MBTA therapy), and has shown promising results in the elimination of subcutaneous murine melanoma, pheochromocytoma, colon carcinoma, and smaller pancreatic adenocarcinoma (Panc02). Here, we tested the short- and long-term effects of MBTA therapy in established subcutaneous Panc02 tumors two times larger than in previous study and bilateral Panc02 models as well as the roles of CD4+ and CD8+ T lymphocytes in this therapy...

The state-of-the-art for melanoma treatment has recently witnessed an enormous revolution, evolving from a chemotherapeutic, "one-drug-for-all" approach, to a tailored molecular- and immunological-based approach with the potential to make personalized therapy a reality. Nevertheless, methods still have to improve a lot before these can reliably characterize all the tumoral features that make each patient unique. While the clinical introduction of next-generation sequencing has made it possible to match mutational profiles to specific targeted therapies, improving response rates to immunotherapy will similarly require a deep understanding of the immune microenvironment and the specific contribution of each component in a patient-specific way...

Melanoma is an extremely malignant tumor with early metastasis and high mortality. Little is known about the process of by which melanoma occurs, as its mechanism is very complex and only limited data are available on its long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs). The purpose of this study was to screen out potential prognostic molecules and identify a ceRNA network related to the occurrence of melanoma. We screened 169 differentially expressed mRNAs (DEmRNAs) from E-MTAB-1862 and GSE3189; gene ontology (GO) enrichment analysis showed that these genes were closely related to the development of skin...

Uveal melanoma (UM) is an aggressive and deadly neoplasm. In recent decades, great efforts have been made to obtain a more comprehensive understanding of genetics, genomics and molecular changes in UM, enabling the identification of key cellular processes and signalling pathways. Still, there is no effective treatment for the metastatic disease. Intratumoural heterogeneity (ITH) is thought to be one of the leading determinants of metastasis, therapeutic resistance and recurrence. Crucially, tumours are complex ecosystems, where cancer cells, and diverse cell types from their microenvironment engage in dynamic spatiotemporal crosstalk that allows cancer progression, adaptation and evolution...

BACKGROUND: Skin cancer is the most common cancer worldwide. OBJECTIVE: To evaluate burden of skin cancer in the US from 1990 to 2019. METHODS: Age-standardized incidence, prevalence, disability adjusted life years (DALY) and mortality rates from skin cancer in the US were evaluated from the Global Burden of Disease (GBD) 2019. RESULTS: Incidence, prevalence, DALY and mortality rates per 100,000 persons from melanoma in 2019 were 17...

The deleterious effects of psychological stress on mainstream T lymphocytes are well documented. However, how stress impacts innate-like T cells is unclear. We report that long-term stress surprisingly abrogates both T helper 1 (TH 1)- and TH 2-type responses orchestrated by invariant natural killer T (iNKT) cells. This is not due to iNKT cell death because these cells are unusually refractory to stress-inflicted apoptosis. Activated iNKT cells in stressed mice exhibit a "split" inflammatory signature and trigger sudden serum interleukin-10 (IL-10), IL-23, and IL-27 spikes...

Purpose : Predictive diagnostics play an increasingly important role in personalized medicine for cancer treatment. Whole genome sequencing (WGS) based treatment selection is expected to rapidly increase worldwide. This study aimed to calculate and compare the total cost of currently used diagnostic techniques and of WGS in treatment of non-small cell lung carcinoma (NSCLC), melanoma, colorectal cancer (CRC) and gastrointestinal stromal tumor (GIST) in the Netherlands. Methods : The activity-based costing (ABC) method was conducted to calculate total cost of included diagnostic techniques based on data provided by Dutch pathology laboratories and the Dutch centralized cancer WGS facility...

Melanoma is a common tumor accounting for around 3&ndash;5% of all cutaneous malignancies with worldwide increasing incidence. It is still associated with significant mortality despite the breakthrough of new innovative therapies within the last decade. A wide variety of treatment modalities is currently used for the management of melanoma, ranging from surgical excision of primary melanoma to adju-vant and palliative treatment with target molecules, including BRAF and MEK inhibitors, and immune checkpoint inhibitors...

No abstract text is available yet for this article.

Last decade brought new achievements in the melanoma research, which resulted in an important changes in the clinical management of stage III melanoma. The article summarizes recent updates with particular focus on practical aspects. Results from surgical studies, Multicenter Selective Lymphadenectomy Trial II (MSLT-II) and German Dermatologic Cooperative Oncology Group (DeCOG-SLT) proved that surgical dogmatic approach that all sentinel node melanoma metastasis warrants completion lymphadenectomy is no longer valid; omission of completion lymphadenectomy in large proportion of sentinel node positive melanoma patients has no negative impact on survival rates...

Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions...

Background: The prognostic value of polybromo 1 ( PBRM1 ) gene mutations in clear cell renal carcinoma (CCRCC) with anti-programmed death-ligand 1 (PD-L1) therapy remains controversial, and few studies have reported the impact of PBRM1 mutations in other cancer types. Methods: The patient information was obtained from cBioPortal and the Tumor Immune Estimation Resource (TIMER) databases. Mann-Whitney U test were used for correlation analysis. For survival analyses, Kaplan-Meier survival curves were used and compared using the log-rank test...

Triple-negative breast cancer (TNBC) cells obtain energy mainly through aerobic glycolysis, and their glycolytic rate is significantly higher compared with that of non-TNBC cells. Glucose transporter 1 (GLUT1) is a transmembrane transporter necessary for the entry of glucose into tumor cells, hexokinase (HK) is a key enzyme in the glycolytic pathway, and both are targets of the transcription factor c-Myc. c-Myc can promote aerobic glycolysis by upregulating GLUT1 expression and enhancing HK activity. c-Myc and GLUT1 are highly expressed in TNBC...

A 47-year-old man presented with profound loss of vision in right eye and relative afferent pupillary defect. On fundus examination, posterior pole details were obscured due to dense vitreous haemorrhage. B-scan ultrasonography was performed that revealed a mushroom-shaped hyperechoic lesion with medium internal reflectivity on A-scan ultrasonography. After performing contrast-enhanced MRI of the orbit, a diagnosis of choroidal melanoma was established. Patient was managed using plaque brachytherapy based on multiplanar MRI...