Molecular Signatures Associated with Prolonged Survival In Melanoma Patients Treated with Dendritic Cell-Based Immunotherapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE106128 | GEO | 2017/10/25
SECONDARY ACCESSION(S): PRJNA415645
REPOSITORIES: GEO
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Project description:Patients affected by stage IV melanoma were subjected to a first round of DC vaccination in two centres, then PBMCs were extracted and mRNA analysed using Illumina arrays for identifying signals related to a favourable outcome of the therapy in terms of survival. A panel of candidate markers was further verified by real time PCR on PBMCs from patients treated with the same vaccination protocol in additional centres. This multi-centric study allowed to identify the gene PEBP1 as a candidate biomarker for vaccination positive outcome. The data released here was used to derive the first panel of markers.
2017-06-01 | E-MTAB-5201 | biostudies-arrayexpress
Project description:Molecular Signatures Associated with Prolonged Survival In Melanoma Patients Treated with Dendritic Cell-Based Immunotherapy
| PRJNA415645 | ENA
Project description:We have study 15 melanoma metastasis obtained from 2 different patients. Five metastases were obtained from patient 1 after M-VAX treatment (2 regressing and 3 progressing). Ten were obtained from patient 2, five after interferon treatment (1 progressing and 4 regreesing) and another 5 after M-VAX treatment (1 progressing and 4 regressing) We have study 15 melanoma metastasis obtained from 2 different patients. Five metastases were obtained from patient 1 after M-VAX treatment (2 regressing and 3 progressing). Ten were obtained from patient 2, five after interferon treatment (1 progressing and 4 regreesing) and another 5 after M-VAX treatment (1 progressing and 4 regressing)
2011-12-31 | E-GEOD-26383 | biostudies-arrayexpress
Project description:In this study, we compared gene expression and genome methylation of diverse fibroblast populations from a patient suffering from acrolentiginous melanoma (Breslow 4.0 mm, Clark IV, B-Raf V600E mutated). Stromal cells from the metastasis, i.e., melanoma associated fibroblasts (MAF), were positive for smooth muscle actin (SMA). Autologous control fibroblasts (ACF) isolated from distant uninvolved skin of the same patient during B-Raf inhibitor therapy and before clinical progression of the disease exhibited also strong SMA expression. Similar phenotype was observed in control dermal fibroblasts (CDF) from different donors yet exclusively after stimulation by TGF-β1. The identified differences in gene transcription as well as in DNA methylation indicate systemic activation of dermal fibroblasts in a patient with malignant melanoma. This dataset contains transcription profiling data, complementary methylation profiling data are available under accession E-MTAB-4965.
2018-12-31 | E-MTAB-4964 | biostudies-arrayexpress
Project description:In this study, we compared gene expression and genome methylation of diverse fibroblast populations from a patient suffering from acrolentiginous melanoma (Breslow 4.0 mm, Clark IV, B-Raf V600E mutated). Stromal cells from the metastasis, i.e., melanoma associated fibroblasts (MAF), were positive for smooth muscle actin (SMA). Autologous control fibroblasts (ACF) isolated from distant uninvolved skin of the same patient during B-Raf inhibitor therapy and before clinical progression of the disease exhibited also strong SMA expression. Similar phenotype was observed in control dermal fibroblasts (CDF) from different donors yet exclusively after stimulation by TGF-β1. The identified differences in gene transcription as well as in DNA methylation indicate systemic activation of dermal fibroblasts in a patient with malignant melanoma. This dataset contains genome methylation profiling data, complementary transcriptome profiling data are available under accession E-MTAB-4964.
2018-12-30 | E-MTAB-4965 | biostudies-arrayexpress
Project description: Not available
| S-EPMC5908302 | biostudies-literature
Project description:Introduction: Infiltration of cancers by T-cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T-cell infiltration of tumors are not known. This study tests the hypothesis that topical treatment of melanoma metastases with the TLR7 agonist imiquimod treatment plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Patients and Methods: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to tumors daily. Adverse events (AE; CTCAE v4.03) were recorded and effects on the tumor microenvironment (TME) were evaluated from sequential tumor biopsies. T-cell responses were assessed by IFNgamma ELIspot assay, and T-cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Results and Conclusions: Four eligible patients were enrolled, and administration of imiquimod and vaccination was well tolerated in these patients. Circulating T-cell responses to the vaccine were detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T-cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. Precis: This clinical trial tested topical application of imiquimod to melanoma metastases combined with a melanoma vaccine. The regimen dramatically upregulated immune rejection gene signatures in melanoma metastases and increased T-cell infiltrate.
2017-04-01 | GSE80028 | GEO
Project description:DNA methylation profiles were recently proposed to have predictive value in various solid tumors. Therefore, we analyzed DNA methylation profiles of patients with stage IV metastatic melanoma, receiving first-line immune checkpoint inhibitors (ICIs) and correlated those with radiological response (iRECIST). Overall, 81 tissue samples from 71 patients with metastatic melanoma (27 (38.0%) female, 44 (62.0%) male) were investigated; median progression free survival was 8.5 months (0 – 104.1 months) and median overall survival was 30.6 months (0 – 104.1 months), respectively. 29 (40.8%) patients achieved an objective response. DNA methylation analyses revealed signatures correlating with radiological response to ICIs. Based on the 500 mostly differentially methylated genes, three clusters were identified with the majority of responders being in cluster 1 (12/12) and cluster 2 (12/24), and non-responders in cluster 3 (39/45). Our findings indicate that tumor DNA methylation profiling may be used as a predictor for ICI-response in patients with metastatic melanoma.
2024-04-03 | GSE235122 | GEO
Project description:Objective: This study aimed to evaluate the effect of dendritic cell (DC) vaccination against HIV-1 on host gene expression profiles. Design: Longitudinal PBMC samples were collected from participants of the DC-TRN trial for immunotherapy against HIV. Microarray-assisted gene expression profiling was performed to evaluate the effects of vaccination and subsequent interruption of antiretroviral therapy on host genome expression. Data from the DC-TRN trial were compared with results from other vaccination trials. Methods: We used Affymetrix GeneChips for microarray gene expression analysis. Data were analyzed by principal component analysis and differential gene expression was assessed using linear modeling. Gene ontology enrichment and gene set analysis were used to characterize differentially expressed genes. Transcriptome analysis included comparison with PBMCs obtained from DC-vaccinated melanoma patients and of healthy individuals who received seasonal influenza vaccination. Results: DC-TRN immunotherapy in HIV-infected individuals resulted in a major shift in the transcriptome. Longitudinal analysis demonstrated that changes in the transcriptome sustained also during interruption of antiretroviral therapy. After DC-vaccination, the transcriptome was enriched for cellular immunity associated genes that were also induced in healthy adults who received live attenuated influenza virus vaccination. These beneficial responses were accompanied by detrimental signals of general immune activation. Conclusions: The DC-TRN induced changes in the transcriptome were profound, lasting, and consisted of both protective signals and signatures of inflammation and immune exhaustion, with a net result of decreased viral load, without clinical benefit. Thus transcriptome analysis provides useful information, dissecting both positive and negative effects, for the evaluation of safety and efficacy of immunotherapeutic strategies.
2015-04-30 | E-MTAB-3296 | biostudies-arrayexpress
Project description:Gene signatures have been shown to predict the response/resistance to immunotherapies but with only modest accuracy. Reduction in this precision might be due to the lack of spatial information which prevents the ability from distinguish tumor from tumor-microenvironment (TME) genes. Here we collected gene expression data spatially from three compartments (CD68+macrophages, CD45+leukocytes and S100+tumor cells) of 59-immunotherapy-treated melanoma specimens using Digital Spatial Profiling-Whole Transcriptome Atlas. We developed a computational pipeline to discover compartment-specific gene signatures and determine if adding spatial information can improve patient stratification. We achieved AUC≥0.90 for CD45, AUC≥0.94 for CD68, and AUC≥0.86 for S100B signatures, whereas AUC≥0.70 for pseudo-bulk () signature. Cross-testing in different compartments (e.g., CD45 signature in CD68 and S100B compartments) showed poor performance indicating compartment-specificity. Our novel spatial S100B signature showed the best performance with AUC≥0.80 in the validation cohort (N=46). Testing our signatures in computationally deconvolved pseudo-compartments revealed lower AUCs. We conclude that the spatially defined compartment signatures utilize tumor and TME-specific information, leading to more accurate prediction of treatment outcome, and thus merit prospective clinical
2023-05-24 | GSE233305 | GEO