PD-L1 (CD274) promoter methylation predicts survival in patients with acute myeloid leukemia

Goltz, Diane; Gevensleben, Heidrun; Grünen, S; Dietrich, Jörn; Kristiansen, Glen; Landsberg, Jennifer; Dietrich, Dimo

doi:10.1038/leu.2016.328

Cited by 69 publications

(59 citation statements)

References 15 publications

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“…Methylation values for each bead pair comprised of a variant specific for the methylated and the unmethylated status, respectively, and were calculated by the formula 100*bead_intensity_methylated/(bead_intensity_methylated+ bead_intensity_ unmethylated) as previously described [32]. Data of level 2 from the TCGA Head and Neck Squamous Cell Carcinoma (TCGA-HNSCC) cohort were downloaded from the TCGA webpage.…”

Section: Methodsmentioning

confidence: 99%

PDCD1 (PD-1) promoter methylation predicts outcome in head and neck squamous cell carcinoma patients

et al. 2017

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BackgroundBiomarkers that facilitate the prediction of disease recurrence in head and neck squamous cell carcinoma (HNSCC) may enable physicians to personalize treatment. In the current study, DNA promoter methylation of programmed cell death 1 (PDCD1, PD-1) was evaluated as a prognostic biomarker in HNSCC patients.ResultsHigh PDCD1 methylation (mPDCD1) was associated with a significantly shorter overall survival after surgical resection in both the discovery (HR = 2.24 [95%CI: 1.08–4.64], p = 0.029) and the validation cohort (HR = 1.54 [95%CI: 1.08–2.21], p = 0.017). In multivariate Cox proportional hazards analysis, PDCD1 methylation remained a significant prognostic factor for HNSCC (HR = 2.14 [95%CI: 1.19–3.84], p = 0.011). Further, mPDCD1 was strongly associated with the human papilloma virus (HPV) status.Materials and MethodsmPDCD1 was assessed retrospectively in a discovery cohort of 120 HNSCC patients treated at the University Hospital of Bonn and a validation cohort of 527 HNSCC cases analyzed by The Cancer Genome Atlas Research Network.ConclusionsPDCD1methylation might aid the identification of HNSCC patients potentially benefitting from a radical or alternative treatment, particularly in the context of immunotherapies targeting PD-1/PD-L1.

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Section: Methodsmentioning

confidence: 99%

PDCD1 (PD-1) promoter methylation predicts outcome in head and neck squamous cell carcinoma patients

et al. 2017

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“…There is therefore an intriguing potential for synergism between expression of cancer antigens, activation of innate interferon response pathways to ERV upregulation, and immune checkpoint blockade in those receiving hypomethylating agents [70]. Hypermethylation of PD-L1 was associated with lower risk for relapse and prolonged overall survival, although this was not an independent risk factor in multivariate analysis with cytogenetics and TP53 mutations [71]. Promoter hypomethylation at the PD-L1 locus in leukemic blasts was correlated to unfavorable cytogenetic risk and TP53 mutations [71].…”

Section: Modulation Of Immune Cell Subsets By Hypomethylating Agentsmentioning

confidence: 99%

Immunological effects of hypomethylating agents

Lindblad

Goswami

Hourigan

et al. 2017

Expert Review of Hematology

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Introduction: Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas Covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert Commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

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“…11 In prostate cancer and acute myeloid leukemia cohorts analyzed by The Cancer Genome Atlas (TCGA), CD274 promoter methylation (mPD-L1) correlates with gene expression and is associated with survival. 12,13 We therefore hypothesized that PD-L1 expression might be under direct epigenetic control in CRC as well and consequently might be of major importance for the stratification of patients potentially benefitting from immunotherapeutic PD-1/PD-L1 checkpoint inhibition.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients

et al. 2016

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This study evaluates promoter methylation of the programmed cell death ligand 1 (PD-L1) as a biomarker in a cohort of 383 colorectal cancer patients. PD-L1 methylation (mPD-L1) was inversely correlated with PD-L1 mRNA expression (p D 0.001) and was associated with significantly shorter overall survival (OS, p D 0.003) and recurrence-free survival (RFS, p < 0.001). In age-stratified multivariate Cox proportional hazards analyses including sex, tumor, nodal, distant metastasis categories, microsatellite instability (MSI)-status, and PD-L1 mRNA, mPD-L1 is classified as an independent prognostic factor (OS: p D 0.030; RFS: p < 0.001). Further studies are needed to evaluate PD-L1 methylation as a biomarker for response prediction of immunotherapies targeting the PD-1/PD-L1 axis.

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PD-L1 (CD274) promoter methylation predicts survival in patients with acute myeloid leukemia

Cited by 69 publications

References 15 publications

PDCD1 (PD-1) promoter methylation predicts outcome in head and neck squamous cell carcinoma patients

PDCD1 (PD-1) promoter methylation predicts outcome in head and neck squamous cell carcinoma patients

Immunological effects of hypomethylating agents

PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients

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