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Immunogenomic identification and characterization of granulocytic myeloid derived suppressor cells in multiple myeloma

ABSTRACT: Immunogenomic identification and characterization of granulocytic myeloid derived suppressor cells in multiple myeloma

PROVIDER: PRJNA630901 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11727500.fastq.gz	Fastqsanger.gz
	SRR11727501.fastq.gz	Fastqsanger.gz
	SRR11727502.fastq.gz	Fastqsanger.gz
	SRR11727503.fastq.gz	Fastqsanger.gz
	SRR11727504.fastq.gz	Fastqsanger.gz

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Immunogenomic identification and characterization of granulocytic myeloid derived suppressor cells in multiple myeloma (ATAC-Seq Neutrophils)

Project description:Purpose: we aimed at providing the phenotypic profile of G-MDSCs based on their prognostic significance in MM, immunosuppressive potential, and molecular program. Methods and results: The pre-established phenotype of G-MDSCs was evaluated in bone marrow samples from controls and MM patients using multidimensional flow cytometry and, surprisingly, we found that CD11b+CD14-CD15+CD33+HLADR- cells overlapped with common eosinophils and neutrophils, which were not expanded in MM patients. Thus, we relied on automated clustering to unbiasedly identify all granulocytic subsets in the tumor microenvironment: basophils, eosinophils, immature, intermediate and mature neutrophils. In a series of 267 newly-diagnosed MM patients (GEM2012MENOS65 trial), only the frequency of mature neutrophils at diagnosis was significantly associated with patients’ outcome, and a high mature-neutrophils/T-cell ratio resulted in inferior progression-free survival (P<.001). Upon FACSorting of each neutrophil subset, T cell proliferation decreased in presence of mature neutrophils (0.5-fold; P=.016) and the cytotoxic potential of T cells engaged by a BCMAxCD3 bispecific antibody increased notably with the depletion of mature neutrophils (4-fold; P=.0007). Most interestingly, RNAseq of the three subsets revealed that G-MDSCs-related genes were specifically upregulated in mature neutrophils from MM patients vs controls due to differential chromatin accessibility. Conclusion: Taken together, we established a correlation between the clinical significance, immunosuppressive potential and transcriptional network of well-defined neutrophil subsets, providing for the first time, a set of optimal markers (CD11b/CD13/CD16) for accurate monitoring of G-MDCSs in MM.

2020-05-08 | GSE150018 | GEO

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2020-05-08 | GSE150021 | GEO

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2020-05-08 | GSE150020 | GEO

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Immunogenomic identification and characterization of granulocytic myeloid derived suppressor cells in multiple myeloma

Project description:This SuperSeries is composed of the SubSeries listed below.

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RNA-seq of human multiple myeloma patients myeloid-derived suppressor cells (M-MDSC)

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