Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset

Autores
Podaza, Enrique Arturo; Risnik, Denise Mariel; Colado, Ana; Elías, Esteban Enrique; Almejún, María Belén; Fernandez Grecco, Horacio; Bezares, Raimundo Fernando; Borge, Mercedes; Gamberale, Romina; Giordano, Mirta Nilda
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Reprogramming of neutrophils by malignant cells is well-described for many types of solid tumors, but data remain scarce for hematological diseases. Chronic lymphocytic leukemia (CLL) is characterized for a deep immune dysregulation mediated by leukemic cells that compromises patient´s outcome. Murine models of CLL highlight the relevance of myeloid cells as tumor-driven reprogramming targets. In our study, we evaluated neutrophil reprogramming by CLL cells. We first show that the proportion of the CD16high CD62Ldim neutrophil subset in peripheral blood of CLL patients is increased compared to age-matched healthy donors (HD). In vitro, neutrophils from HD cultured in the presence of CLL cells or conditioned media (CM) from CLL cells exhibited a longer lifespan. Depletion of G-CSF and GM-CSF from CM partially reversed the protective effect. In addition, the proportion of viable neutrophils that displayed a CD16high CD62Ldim phenotype was increased in the presence of CM from CLL cells, being TGF-β/IL-10 responsible for this effect. Altogether, our results describe a novel mechanism through which CLL cells can manipulate neutrophils.
Fil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Risnik, Denise Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Colado, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Elías, Esteban Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Almejún, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fernandez Grecco, Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bezares, Raimundo Fernando. Sanatorio Municipal "Dr. Julio Mendez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; Argentina
Fil: Borge, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
TUMOR ASSOCIATED NEUTROPHILS
APOPTOSIS
REPROGRAMMING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/103571
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/103571
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subsetPodaza, Enrique ArturoRisnik, Denise MarielColado, AnaElías, Esteban EnriqueAlmejún, María BelénFernandez Grecco, HoracioBezares, Raimundo FernandoBorge, MercedesGamberale, RominaGiordano, Mirta NildaTUMOR ASSOCIATED NEUTROPHILSAPOPTOSISREPROGRAMMINGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Reprogramming of neutrophils by malignant cells is well-described for many types of solid tumors, but data remain scarce for hematological diseases. Chronic lymphocytic leukemia (CLL) is characterized for a deep immune dysregulation mediated by leukemic cells that compromises patient´s outcome. Murine models of CLL highlight the relevance of myeloid cells as tumor-driven reprogramming targets. In our study, we evaluated neutrophil reprogramming by CLL cells. We first show that the proportion of the CD16high CD62Ldim neutrophil subset in peripheral blood of CLL patients is increased compared to age-matched healthy donors (HD). In vitro, neutrophils from HD cultured in the presence of CLL cells or conditioned media (CM) from CLL cells exhibited a longer lifespan. Depletion of G-CSF and GM-CSF from CM partially reversed the protective effect. In addition, the proportion of viable neutrophils that displayed a CD16high CD62Ldim phenotype was increased in the presence of CM from CLL cells, being TGF-β/IL-10 responsible for this effect. Altogether, our results describe a novel mechanism through which CLL cells can manipulate neutrophils.Fil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Risnik, Denise Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Colado, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Elías, Esteban Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Almejún, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fernandez Grecco, Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bezares, Raimundo Fernando. Sanatorio Municipal "Dr. Julio Mendez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; ArgentinaFil: Borge, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaJohn Wiley & Sons Inc2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/103571Podaza, Enrique Arturo; Risnik, Denise Mariel; Colado, Ana; Elías, Esteban Enrique; Almejún, María Belén; et al.; Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset; John Wiley & Sons Inc; International Journal of Cancer. Journal International du Cancer; 144; 5; 9-2019; 1128-11340020-7136CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/ijc.31762info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31762info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:29:28Zoai:ri.conicet.gov.ar:11336/103571instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:29:29.089CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset
title Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset
spellingShingle Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset
Podaza, Enrique Arturo
TUMOR ASSOCIATED NEUTROPHILS
APOPTOSIS
REPROGRAMMING
title_short Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset
title_full Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset
title_fullStr Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset
title_full_unstemmed Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset
title_sort Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset
dc.creator.none.fl_str_mv Podaza, Enrique Arturo
Risnik, Denise Mariel
Colado, Ana
Elías, Esteban Enrique
Almejún, María Belén
Fernandez Grecco, Horacio
Bezares, Raimundo Fernando
Borge, Mercedes
Gamberale, Romina
Giordano, Mirta Nilda
author Podaza, Enrique Arturo
author_facet Podaza, Enrique Arturo
Risnik, Denise Mariel
Colado, Ana
Elías, Esteban Enrique
Almejún, María Belén
Fernandez Grecco, Horacio
Bezares, Raimundo Fernando
Borge, Mercedes
Gamberale, Romina
Giordano, Mirta Nilda
author_role author
author2 Risnik, Denise Mariel
Colado, Ana
Elías, Esteban Enrique
Almejún, María Belén
Fernandez Grecco, Horacio
Bezares, Raimundo Fernando
Borge, Mercedes
Gamberale, Romina
Giordano, Mirta Nilda
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TUMOR ASSOCIATED NEUTROPHILS
APOPTOSIS
REPROGRAMMING
topic TUMOR ASSOCIATED NEUTROPHILS
APOPTOSIS
REPROGRAMMING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Reprogramming of neutrophils by malignant cells is well-described for many types of solid tumors, but data remain scarce for hematological diseases. Chronic lymphocytic leukemia (CLL) is characterized for a deep immune dysregulation mediated by leukemic cells that compromises patient´s outcome. Murine models of CLL highlight the relevance of myeloid cells as tumor-driven reprogramming targets. In our study, we evaluated neutrophil reprogramming by CLL cells. We first show that the proportion of the CD16high CD62Ldim neutrophil subset in peripheral blood of CLL patients is increased compared to age-matched healthy donors (HD). In vitro, neutrophils from HD cultured in the presence of CLL cells or conditioned media (CM) from CLL cells exhibited a longer lifespan. Depletion of G-CSF and GM-CSF from CM partially reversed the protective effect. In addition, the proportion of viable neutrophils that displayed a CD16high CD62Ldim phenotype was increased in the presence of CM from CLL cells, being TGF-β/IL-10 responsible for this effect. Altogether, our results describe a novel mechanism through which CLL cells can manipulate neutrophils.
Fil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Risnik, Denise Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Colado, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Elías, Esteban Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Almejún, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fernandez Grecco, Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bezares, Raimundo Fernando. Sanatorio Municipal "Dr. Julio Mendez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; Argentina
Fil: Borge, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Reprogramming of neutrophils by malignant cells is well-described for many types of solid tumors, but data remain scarce for hematological diseases. Chronic lymphocytic leukemia (CLL) is characterized for a deep immune dysregulation mediated by leukemic cells that compromises patient´s outcome. Murine models of CLL highlight the relevance of myeloid cells as tumor-driven reprogramming targets. In our study, we evaluated neutrophil reprogramming by CLL cells. We first show that the proportion of the CD16high CD62Ldim neutrophil subset in peripheral blood of CLL patients is increased compared to age-matched healthy donors (HD). In vitro, neutrophils from HD cultured in the presence of CLL cells or conditioned media (CM) from CLL cells exhibited a longer lifespan. Depletion of G-CSF and GM-CSF from CM partially reversed the protective effect. In addition, the proportion of viable neutrophils that displayed a CD16high CD62Ldim phenotype was increased in the presence of CM from CLL cells, being TGF-β/IL-10 responsible for this effect. Altogether, our results describe a novel mechanism through which CLL cells can manipulate neutrophils.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/103571
Podaza, Enrique Arturo; Risnik, Denise Mariel; Colado, Ana; Elías, Esteban Enrique; Almejún, María Belén; et al.; Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset; John Wiley & Sons Inc; International Journal of Cancer. Journal International du Cancer; 144; 5; 9-2019; 1128-1134
0020-7136
CONICET Digital
CONICET
url http://hdl.handle.net/11336/103571
identifier_str_mv Podaza, Enrique Arturo; Risnik, Denise Mariel; Colado, Ana; Elías, Esteban Enrique; Almejún, María Belén; et al.; Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16 high CD62L dim immunosuppressive subset; John Wiley & Sons Inc; International Journal of Cancer. Journal International du Cancer; 144; 5; 9-2019; 1128-1134
0020-7136
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/ijc.31762
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31762
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv John Wiley & Sons Inc
publisher.none.fl_str_mv John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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