Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.

Tumour-draining lymph nodes (LNs) undergo massive remodelling including expansion of the lymphatic sinuses, a process that has been linked to lymphatic metastasis by creation of a pre-metastatic niche. However, the signals leading to these changes have not been completely understood. Here, we found...

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Detalles Bibliográficos
Autores: Leary, Noelle, Walser, Sarina, He, Yuliang, Cousin, Nikola, Pereira, Paulo, Gallo, Alessandro, Collado-Diaz, Victor, Halin, Cornelia, Garcia-Silva, Susana, Peinado Selgas, Hector, Dieterich, Lothar C
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/27254
Acceso en línea:https://hdl.handle.net/20.500.12105/27254
Access Level:acceso abierto
Palabra clave:exosome
immunotherapy
lymphangiogenesis
pre-metastatic niche
sentinel lymph node
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spelling Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.Leary, NoelleWalser, SarinaHe, YuliangCousin, NikolaPereira, PauloGallo, AlessandroCollado-Diaz, VictorHalin, CorneliaGarcia-Silva, SusanaPeinado Selgas, HectorDieterich, Lothar Cexosomeimmunotherapylymphangiogenesispre-metastatic nichesentinel lymph nodeTumour-draining lymph nodes (LNs) undergo massive remodelling including expansion of the lymphatic sinuses, a process that has been linked to lymphatic metastasis by creation of a pre-metastatic niche. However, the signals leading to these changes have not been completely understood. Here, we found that extracellular vesicles (EVs) derived from melanoma cells are rapidly transported by lymphatic vessels to draining LNs, where they selectively interact with lymphatic endothelial cells (LECs) as well as medullary sinus macrophages. Interestingly, uptake of melanoma EVs by LN-resident LECs was partly dependent on lymphatic VCAM-1 expression, and induced transcriptional changes as well as proliferation of those cells. Furthermore, melanoma EVs shuttled tumour antigens to LN LECs for cross-presentation on MHC-I, resulting in apoptosis induction in antigen-specific CD8 T cells. In conclusion, our data identify EV-mediated melanoma-LN LEC communication as a new pathway involved in tumour progression and tumour immune inhibition, suggesting that EV uptake or effector mechanisms in LECs might represent a new target for melanoma therapy.Wiley20262026-02-2120222022-02-0120222022-02-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12105/27254reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/272542026-06-12T12:43:37Z
dc.title.none.fl_str_mv Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
title Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
spellingShingle Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
Leary, Noelle
exosome
immunotherapy
lymphangiogenesis
pre-metastatic niche
sentinel lymph node
title_short Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
title_full Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
title_fullStr Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
title_full_unstemmed Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
title_sort Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.
dc.creator.none.fl_str_mv Leary, Noelle
Walser, Sarina
He, Yuliang
Cousin, Nikola
Pereira, Paulo
Gallo, Alessandro
Collado-Diaz, Victor
Halin, Cornelia
Garcia-Silva, Susana
Peinado Selgas, Hector
Dieterich, Lothar C
author Leary, Noelle
author_facet Leary, Noelle
Walser, Sarina
He, Yuliang
Cousin, Nikola
Pereira, Paulo
Gallo, Alessandro
Collado-Diaz, Victor
Halin, Cornelia
Garcia-Silva, Susana
Peinado Selgas, Hector
Dieterich, Lothar C
author_role author
author2 Walser, Sarina
He, Yuliang
Cousin, Nikola
Pereira, Paulo
Gallo, Alessandro
Collado-Diaz, Victor
Halin, Cornelia
Garcia-Silva, Susana
Peinado Selgas, Hector
Dieterich, Lothar C
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv exosome
immunotherapy
lymphangiogenesis
pre-metastatic niche
sentinel lymph node
topic exosome
immunotherapy
lymphangiogenesis
pre-metastatic niche
sentinel lymph node
description Tumour-draining lymph nodes (LNs) undergo massive remodelling including expansion of the lymphatic sinuses, a process that has been linked to lymphatic metastasis by creation of a pre-metastatic niche. However, the signals leading to these changes have not been completely understood. Here, we found that extracellular vesicles (EVs) derived from melanoma cells are rapidly transported by lymphatic vessels to draining LNs, where they selectively interact with lymphatic endothelial cells (LECs) as well as medullary sinus macrophages. Interestingly, uptake of melanoma EVs by LN-resident LECs was partly dependent on lymphatic VCAM-1 expression, and induced transcriptional changes as well as proliferation of those cells. Furthermore, melanoma EVs shuttled tumour antigens to LN LECs for cross-presentation on MHC-I, resulting in apoptosis induction in antigen-specific CD8 T cells. In conclusion, our data identify EV-mediated melanoma-LN LEC communication as a new pathway involved in tumour progression and tumour immune inhibition, suggesting that EV uptake or effector mechanisms in LECs might represent a new target for melanoma therapy.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-02-01
2022
2022-02-01
2026
2026-02-21
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/27254
url https://hdl.handle.net/20.500.12105/27254
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406504964063232
score 15.81155

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