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The aim of this study is to determine the significance of programmed death-ligand 1 (PD-L1 or CD274) methylation in relation to PD-L1 expression and survival in melanoma. Despite the clinical importance of therapies targeting the PD-1/PD-L1 immune checkpoint in melanoma, factors regulating PD-L1 expression, including epigenetic mechanisms, are not completely understood. In this study, we examined PD-L1 promoter methylation in relation to PD-L1 expression and overall survival in melanoma patients. Our results suggest that DNA methylation regulates PD-L1 expression in melanoma, and we identify the key methylated CpG loci in the PD-L1 promoter, establish PD-L1 methylation as an independent survival prognostic factor, provide proof-of-concept for altering PD-L1 expression by hypomethylating agents, and uncover that PD-L1 methylation is associated with an interferon-signaling transcriptional phenotype. Based on our findings, measuring and altering PD-L1 promoter DNA methylation may have potential prognostic and therapeutic applications in melanoma. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Pigment cell & melanoma research
Melanocortin 1 receptor (MC1R) is a G protein-coupled receptor expressed in melanocytes where it plays an important role in skin pigmentation and the UV response, and has implications in melanoma deve...
Constitutive expression of the immune checkpoint, PD-L1, inhibits anti-tumor immune responses in cancer, although the factors involved in PD-L1 regulation are poorly understood. Here we show that loss...
As an important epigenetic modification DNA methylation is catalyzed by DNA methylation transferases (DNMTs) and occurs mainly in CpG islands. DNA methylation plays an important role in regulates gene...
Despite improvements in melanoma mortality, disparities in melanoma survival persist. We evaluated possible sociodemographic and healthcare-based predictors of differences in U.S. melanoma survival us...
Factors influencing melanoma survival include sex, age, clinical stage, lymph node involvement, as well as Breslow thickness, presence of tumor-infiltrating lymphocytes based on histological analysis ...
The goal of this clinical research study is to learn if temozolomide alone or given with pegylated interferon alpha-2b can help to control metastatic melanoma. Researchers also want to stu...
Objectives: The purpose of this study was to assess the long-term follow-up of the overall and melanoma-specific survival in the randomised, open-lable multicenter trial (NTC NCT01183936) ...
This study is divided into distinct sample collection and analysis phases. In the sample collection phase investigators will tape strip lesions that are designated for biopsy because they ...
The maintenance of health and the progression of disease are associated with an individual's genetic make-up and environmental factors, including lifestyle choices (such as diet, exercise,...
Periodontitis is related to host genetics, constitution of the dental biofilm and environmental factors such as smoking. DNA methylation is a mechanism of genetic expression that can inhib...
A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.
An unpigmented malignant melanoma. It is an anaplastic melanoma consisting of cells derived from melanoblasts but not forming melanin. (Dorland, 27th ed; Stedman, 25th ed)
A basic leucine zipper transcription factor that regulates expression of MHC CLASS II GENES through its binding to a conserved X-box DNA sequence in the promoter region. It regulates the expression of genes involved in the UNFOLDED PROTEIN RESPONSE.
A DNA-binding orphan nuclear receptor that positively regulates expression of ARNTL TRANSCRIPTION FACTORS and is a regulatory component of the circadian clock system. The protein also has a role in neuron cell survival and differentiation in that loss of function mutations of its gene result in the mouse phenotype referred to as the STAGGERER MOUSE.
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.
Melanoma is a highly malignant tumor of melanin-forming cells (melanocytes) There are most commonly found in the skin (resulting from sunlight exposure), but also in the eyes and mucous membranes. Metastasis to other regions of the body is also common....
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Basal cell carcinoma Basal cell carcinoma, or BCC, is a cancer of the basal cells at the bottom of the epidermis. It’s very common ...