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Gassmann, H.* ; Schneider, K.* ; Evdokimova, V.* ; Ruzanov, P.* ; Schober, S.J.* ; Xue, B.* ; von Heyking, K.* ; Thiede, M.* ; Richter, G.H.S.* ; Pfaffl, M.W.* ; Nössner, E. ; Stein, L.D.* ; Sorensen, P.H.B.* ; Thiel, U.*

Ewing sarcoma-derived extracellular vesicles impair dendritic cell maturation and function.

Cells 10:2081 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration and predominance of immunosuppressive myeloid cells. Given the important roles of extracellular vesicles (EVs) in cancer-host crosstalk, we hypothesized that EVs secreted by EwS tumors target myeloid cells and promote immunosuppressive phenotypes. Here, EVs were purified from EwS and fibroblast cell lines and exhibited characteristics of small EVs, including size (100-170 nm) and exosome markers CD63, CD81, and TSG101. Treatment of healthy donor-derived CD33+ and CD14+ myeloid cells with EwS EVs but not with fibroblast EVs induced pro-inflammatory cytokine release, including IL-6, IL-8, and TNF. Furthermore, EwS EVs impaired differentiation of these cells towards monocytic-derived dendritic cells (moDCs), as evidenced by reduced expression of co-stimulatory molecules CD80, CD86 and HLA-DR. Whole transcriptome analysis revealed activation of gene expression programs associated with immunosuppressive phenotypes and pro-inflammatory responses. Functionally, moDCs differentiated in the presence of EwS EVs inhibited CD4+ and CD8+ T cell proliferation as well as IFNγ release, while inducing secretion of IL-10 and IL-6. Therefore, EwS EVs may promote a local and systemic pro-inflammatory environment and weaken adaptive immunity by impairing the differentiation and function of antigen-presenting cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Ewing Sarcoma ; Dendritic Cells ; Extracellular Vesicles ; Immunosuppression ; Inflammation ; Myeloid Cells ; Tumor Microenvironment; Immune-responses; Myeloid Cells; Exosomes; Differentiation; Inflammation; Expression; Landscape; Secretion; Cytokines; Promote
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Zeitschrift Cells
Quellenangaben Band: 10, Heft: 8, Seiten: , Artikelnummer: 2081 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Institut(e) Institute of Virology (VIRO)
Förderungen TUM School of Medicine, KKF clinician scientist program