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E-MTAB-6214

ABSTRACT: Bulk RNA-seq validation experiment comparing blood from healthy donors and two groups of metastatic melanoma patients: responders and non-responders to anti-PD-1 immunotherapy

DISEASE(S): Metastatic Melanoma,Normal

PROVIDER: E-MTAB-6214 | ExpressionAtlas | 2025-01-23

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-MTAB-6214-analysis-methods.tsv	Tabular
	E-MTAB-6214-analytics.tsv	Tabular
	E-MTAB-6214-atlasExperimentSummary.Rdata	Rdata
	E-MTAB-6214-configuration.xml	Xml
	E-MTAB-6214-g1_g2-mvaPlot.png	Other

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Project description:Immune checkpoint blockade has revolutionized cancer therapy. In particular, inhibition of programmed cell death protein 1 (PD-1) is effective for the treatment of metastatic melanoma and other cancers. Despite a dramatic increase in progression-free survival, a large proportion of patients do not show durable response. Therefore, predictive biomarkers of clinical response are urgently needed. Here, we employed high-dimensional single cell mass cytometry and a bioinformatics pipeline for the in-depth characterization of the immune cell subsets in the peripheral blood of metastatic melanoma patients before and after anti-PD-1 immunotherapy. During therapy, we observed a clear treatment response to immunotherapy in the T cell compartment. However, prior to commending therapy a strong predictor of progression free and overall survival in response to anti-PD-1 immunotherapy was the frequency of CD14+CD16-HLA-DRhi monocytes. We could confirm this by conventional flow cytometry in an independent validation cohort and propose this as a novel predictive biomarker for therapy decisions in the clinic. In order to determine whether there are cell intrinsic changes in the monocyte signature, we performed RNA sequencing on sorted CD14+CD16-HLA-DRhi cells from HD, NR and R at baseline. Representative samples (n=4, each) of responders/non responders/ and healthy donors were selected from archival samples stored in the dermatology biobank according to the same clinical criteria used in the discovery and validation cohorts for CyTOF and FACS analysis. CD14+CD16-HLA-DRhiLin- (CD3, CD4, CD19, CD45RO) monocytes were sorted from frozen PBMC form blood samples from HD, R and NR at baseline.

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microbiome

Project description:Commensal microbiota associated with anti-PD-1 efficacy in metastatic melanoma patients

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