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dc.contributor.author
Gargiulo, Ernesto
dc.contributor.author
Viry, Elodie
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Morande, Pablo Elías
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dc.contributor.author
Largeot, Anne
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Gonder, Susanne
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Xian, Feng
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Ionnou, Nikolaos
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Benzarti, Mohaned
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Borgmann, Felix Kleine
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Mittelbronn, Michel
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Dittmar, Gunnar
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Nazarov, Petr V.
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Meiser, Johannes
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Stamatopoulos, Basile
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Ramsay, Alan G.
dc.date.available
2024-02-22T13:53:00Z
dc.date.issued
2023-01
dc.identifier.citation
Gargiulo, Ernesto; Viry, Elodie; Morande, Pablo Elías; Largeot, Anne; Gonder, Susanne; et al.; Extracellular Vesicle Secretion by Leukemia Cells In Vivo Promotes CLL Progression by Hampering Antitumor T-cell Responses; American Association for Cancer Research Inc.; Blood Cancer Discovery; 4; 1; 1-2023; 54-77
dc.identifier.issn
2643-3230
dc.identifier.uri
http://hdl.handle.net/11336/228059
dc.description.abstract
Small extracellular vesicle (sEV, or exosome) communication among cells in the tumor microenvironment has been modeled mainly in cell culture, whereas their relevance in cancer pathogenesis and progression in vivo is less characterized. Here we investigated cancer-microenvironment interactions in vivo using mouse models of chronic lymphocytic leukemia (CLL). sEVs isolated directly from CLL tissue were enriched in specific miRNA and immune-checkpoint ligands. Distinct molecular components of tumor-derived sEVs altered CD8+ T-cell transcriptome, proteome, and metabolome, leading to decreased functions and cell exhaustion ex vivo and in vivo. Using antagomiRs and blocking antibodies, we defined specific cargo-mediated alterations on CD8+ T cells. Abrogating sEV biogenesis by Rab27a/b knockout dramatically delayed CLL pathogenesis. This phenotype was rescued by exogenous leukemic sEV or CD8+ T-cell depletion. Finally, high expression of sEV-related genes correlated with poor outcomes in CLL patients, suggesting sEV profiling as a prognostic tool. In conclusion, sEVs shape the immune microenvironment during CLL progression.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Association for Cancer Research Inc.
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Small extracellular vesicle
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Leukemia Cells
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Antitumor T-cell Responses
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Hamper
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Patología
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Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Extracellular Vesicle Secretion by Leukemia Cells In Vivo Promotes CLL Progression by Hampering Antitumor T-cell Responses
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-02-20T13:22:12Z
dc.identifier.eissn
2643-3249
dc.journal.volume
4
dc.journal.number
1
dc.journal.pagination
54-77
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Filadelfia
dc.description.fil
Fil: Gargiulo, Ernesto. Luxembourg Institute Of Health; Luxemburgo
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Fil: Viry, Elodie. Luxembourg Institute Of Health; Luxemburgo
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Fil: Morande, Pablo Elías. Luxembourg Institute Of Health; Luxemburgo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Largeot, Anne. Luxembourg Institute Of Health; Luxemburgo
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Fil: Gonder, Susanne. Luxembourg Institute Of Health; Luxemburgo
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Fil: Xian, Feng. Luxembourg Institute Of Health; Luxemburgo
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Fil: Ionnou, Nikolaos. Centre Hospitalier de Luxembourg; Luxemburgo
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Fil: Benzarti, Mohaned. Luxembourg Institute Of Health; Luxemburgo
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Fil: Borgmann, Felix Kleine. University of Luxembourg; Luxemburgo. Luxembourg Institute Of Health; Luxemburgo
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Fil: Mittelbronn, Michel. University of Luxembourg; Luxemburgo
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Fil: Dittmar, Gunnar. Luxembourg Institute Of Health; Luxemburgo
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Fil: Nazarov, Petr V.. Luxembourg Institute Of Health; Luxemburgo
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Fil: Meiser, Johannes. Luxembourg Institute Of Health; Luxemburgo
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Fil: Stamatopoulos, Basile. Université Libre de Bruxelles; Bélgica
dc.description.fil
Fil: Ramsay, Alan G.. King's College London; Reino Unido
dc.journal.title
Blood Cancer Discovery
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://aacrjournals.org/bloodcancerdiscov/article/4/1/54/712653/Extracellular-Vesicle-Secretion-by-Leukemia-Cells
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1158/2643-3230.BCD-22-0029
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