Similar Datasets
Project description:PD-L1 is a ligand for the inhibitory PD1 receptor on T cells and its expression in some cancers inhibits anti-cancer immune response. In melanoma, PD-L1 expression is induced in response to immune stimuli but in a proportion of melanomas it is constitutively expressed. Factors that drive constitutive expression of PD-L1 are unknown. Here we performed genome-scale methylation analysis of six cell lines that constitutively express PD-L1 (PD-L1 positive, referred to as PD-L1CON) and six cell lines that only express PD-L1 after treatment with IFN- (PD-L1 negative, referred to as PD-L1IND)
2018-05-24 | GSE107621 | GEO
Project description:PD-L1 is a ligand for the inhibitory PD1 receptor on T cells and its expression in some cancers inhibits anti-cancer immune response. In melanoma, PD-L1 expression is induced in response to immune stimuli but in a proportion of melanomas it is constitutively expressed. Factors that drive constitutive expression of PD-L1 are unknown. Here we performed RNA-Seq analysis of six cell lines that constitutively express PD-L1 (PD-L1 positive, referred to as PD-L1CON) and six cell lines that only express PD-L1 after treatment with IFN- (PD-L1 negative, referred to as PD-L1IND)
2018-05-24 | GSE107620 | GEO
Project description:Global hypomethylation mediated changes regulate constitutive PD-L1 expression in melanoma
| PRJNA420852 | ENA
Project description:Global hypomethylation mediated changes regulate constitutive PD-L1 expression in melanoma [RRBS]
| PRJNA420862 | ENA
Project description: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 of global DNA methylation, particularly in intergenic regions and repeat elements, is associated with constitutive (PD-L1CON), versus inducible (PD-L1IND), PD-L1 expression in melanoma cell lines. We further show this is accompanied by transcriptomic up-regulation. De novo epigenetic regulators (e.g., DNMT3A) are strongly correlated with PD-L1 expression and methylome status. Accordingly, decitabine-mediated inhibition of global methylation in melanoma cells leads to increased PD-L1 expression. Moreover, viral mimicry and immune response genes are highly expressed in lymphocyte-negative plus PD-L1-positive melanomas, versus PD-L1-negative melanomas in The Cancer Genome Atlas (TCGA). In summary, using integrated genomic analysis we identified that global DNA methylation influences PD-L1 expression in melanoma, and hence melanoma's ability to evade anti-tumor immune responses. These results have implications for combining epigenetic therapy with immunotherapy.
| S-EPMC6147024 | biostudies-literature
Project description:Global hypomethylation mediated changes regulate constitutive PD-L1 expression in melanoma [RNA-Seq]
| PRJNA420861 | ENA
Project description:Oncogenic driver mutations in several tumor types promote constitutive PD-L1 expression, a crucial ligand in PD-1-mediated tumor immune escape. Our studies in melanoma suggest a different mechanism-one of "adaptive immune resistance" in which PD-L1 expression is primarily driven by cytokine induction and is independent of BRAF mutational status.
| S-EPMC4589064 | biostudies-literature
Project description:BackgroundDPY30 is a common subunit of the human SET1/MLL complex and is an essential protein required for the activity of SET1/MLL methyltransferase. DPY30 regulates the histone H3K4 modification, and dysfunction of DPY30 might contribute to the regulation of cancer immune evasion. However, the functions and regulation of DPY30 in the expression of programmed cell death ligand 1 (PD-L1) is still not completely explored.MethodsVarious online databases were used for data processing and visualization, including UALCAN, Oncomine, cBioPortal, SangerBox, TISIDB, TIMER, and GEPIA databases. The expression of DPY30 and PD-L1 in melanoma tissues were evaluated by IHC. Chromatin Immunoprecipitation (ChIP), RT-PCR and flow cytometry were used to elucidate the underlying molecular mechanism of PD-L1 expression regulation and its function.ResultsThe mRNA level of DPY30 in melanoma was higher than in normal tissues. The expression of DPY30 was positively associated with TMB, neoantigens and PD-L1 expression. Furthermore, DPY30 expression showed significant positive correlations with immune suppressor cells and ICP genes involved in T-cell exhaustion. IHC showed that the positive rates of DPY30 and PD-L1 in melanoma tissues were 62% and 58%, respectively. Correlation analysis revealed that DPY30 over-expression was positively associated with PD-L1 expression. Silencing of DPY30 by specific siRNA significantly inhibited PD-L1 expression. ChIP analysis revealed that H3K4me3 levels were enriched in the proximal PD-L1 promoter region in tumor cells. Inhibition of DPY30 still suppressed the PD-L1 level in IFN-γ treated MMAC-SF cells. Furthermore, the apoptosis of PD1+ T-cells in co-culture with MMAC-SF cells by knockdown of DPY30 were markedly reduced.ConclusionThis study shows the roles of DPY30 in regulating the cancer immune evasion in melanoma. Targeting the DPY30-H3K4me3 axis might be an alternative approach to enhance the efficacy of checkpoint immunotherapy.
| S-EPMC9525212 | biostudies-literature
Project description:Melanoma is the most serious form of skin cancer. Metastatic melanoma historically carries a poor prognosis and until recently there have been few effective agents available to treat widely disseminated disease. Recognition of the immunogenic nature of melanoma has resulted in the development of various immunotherapeutic approaches, especially with regards to the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1). Antibodies targeting the PD-1 axis have shown enormous potential in the treatment of metastatic melanoma. Here, we will review the immune basis for the disease and discuss approved immunotherapeutic options for advanced melanoma, as well as the current state of development of PD-1 and PD-L1 antibodies and their importance in shaping the future of melanoma treatment.
| S-EPMC4514131 | biostudies-literature
Project description:Blocking the PD-1/PD-L1 immunosuppressive pathway has shown promise in the treatment of certain cancers including melanoma. This study investigates differences in the gene expression profiles of human melanomas that do or do not display the immunosuppressive protein PD-L1. Further understanding of genes expressed within the tumor microenvironment of PD-L1+ tumors may lead to improved rationally designed treatments. Gene expression profiling was performed on total RNA extracted by laser capture microdissection from 11 archived formalin-fixed paraffin-embedded (FFPE) melanoma specimens, 5 of which were PD-L1 positive and 6 PD-L1 negative. Details of the design, and the gene signatures found are given in the paper associated with this GEO Series: Janis M. Taube, Geoffrey D. Young, Tracee L. McMiller, Shuming Chen, January T. Salas, Theresa S. Pritchard, Haiying Xu, Alan K. Meeker, Jinshui Fan, Chris Cheadle, Alan E. Berger, Drew M. Pardoll, and Suzanne L. Topalian, Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma: implications for PD-1 pathway blockade, Clin Cancer Res 2015, in press.
2015-05-01 | E-GEOD-65041 | biostudies-arrayexpress