Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin

Autores
Dusoswa, Sophie A.; Verhoeff, Jan; Abels, Erik; Mendez Huergo, Santiago Patricio; Croci Russo, Diego Omar; Kuijper, Lisan H.; de Miguel, Elena; Wouters, Valerie M. C. J.; Best, Myron G.; Rodriguez, Ernesto; Cornelissen, Lenneke A.M.; van Vliet, Sandra J.; Wesseling, Pieter; Breakefield, Xandra O.; Noske, David P.; Würdinger, Thomas; Broekman, Marike L.D.; Rabinovich, Gabriel Adrián; van Kooyk, Yvette; Garcia Vallejo, Juan J.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), which are key mediators of immune suppression and resistance to immunotherapy. We and others demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans trigger inhibitory signaling in TAMs through glycan-binding receptors. We investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. We detected increased expression of both tumor-associated truncated O-linked glycans and their receptor, macrophage galactose-type lectin (MGL), on CD163+ TAMs in glioblastoma patient-derived tumor tissues. In an immunocompetent orthotopic glioma mouse model overexpressing truncated O-linked glycans (MGL ligands), high-dimensional mass cytometry revealed a wide heterogeneity of infiltrating myeloid cells with increased infiltration of PD-L1+ TAMs as well as distant alterations in the bone marrow (BM). Our results demonstrate that glioblastomas exploit cell surface O-linked glycans for local and distant immune modulation.
Fil: Dusoswa, Sophie A.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Verhoeff, Jan. Vrije Universiteit Amsterdam; Países Bajos
Fil: Abels, Erik. Vrije Universiteit Amsterdam; Países Bajos
Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Kuijper, Lisan H.. Vrije Universiteit Amsterdam; Países Bajos
Fil: de Miguel, Elena. Vrije Universiteit Amsterdam; Países Bajos
Fil: Wouters, Valerie M. C. J.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Best, Myron G.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Rodriguez, Ernesto. Vrije Universiteit Amsterdam; Países Bajos
Fil: Cornelissen, Lenneke A.M.. Vrije Universiteit Amsterdam; Países Bajos
Fil: van Vliet, Sandra J.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Wesseling, Pieter. Vrije Universiteit Amsterdam; Países Bajos
Fil: Breakefield, Xandra O.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Noske, David P.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Würdinger, Thomas. Harvard Medical School; Estados Unidos
Fil: Broekman, Marike L.D.. Harvard Medical School; Estados Unidos
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: van Kooyk, Yvette. Vrije Universiteit Amsterdam; Países Bajos
Fil: Garcia Vallejo, Juan J.. Vrije Universiteit Amsterdam; Países Bajos
Materia
GLIOBLASTOMA
IMMUNOSUPPRESSION
MACROPHAGE GALACTOSE LECTIN
MACROPHAGES
O-LINKED GLYCOSYLATION
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:11336/143794
Acceder
id CONICETDig_acf772d82424b16ecd80d9911aff9f95
oai_identifier_str oai:ri.conicet.gov.ar:11336/143794
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectinDusoswa, Sophie A.Verhoeff, JanAbels, ErikMendez Huergo, Santiago PatricioCroci Russo, Diego OmarKuijper, Lisan H.de Miguel, ElenaWouters, Valerie M. C. J.Best, Myron G.Rodriguez, ErnestoCornelissen, Lenneke A.M.van Vliet, Sandra J.Wesseling, PieterBreakefield, Xandra O.Noske, David P.Würdinger, ThomasBroekman, Marike L.D.Rabinovich, Gabriel Adriánvan Kooyk, YvetteGarcia Vallejo, Juan J.GLIOBLASTOMAIMMUNOSUPPRESSIONMACROPHAGE GALACTOSE LECTINMACROPHAGESO-LINKED GLYCOSYLATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), which are key mediators of immune suppression and resistance to immunotherapy. We and others demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans trigger inhibitory signaling in TAMs through glycan-binding receptors. We investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. We detected increased expression of both tumor-associated truncated O-linked glycans and their receptor, macrophage galactose-type lectin (MGL), on CD163+ TAMs in glioblastoma patient-derived tumor tissues. In an immunocompetent orthotopic glioma mouse model overexpressing truncated O-linked glycans (MGL ligands), high-dimensional mass cytometry revealed a wide heterogeneity of infiltrating myeloid cells with increased infiltration of PD-L1+ TAMs as well as distant alterations in the bone marrow (BM). Our results demonstrate that glioblastomas exploit cell surface O-linked glycans for local and distant immune modulation.Fil: Dusoswa, Sophie A.. Vrije Universiteit Amsterdam; Países BajosFil: Verhoeff, Jan. Vrije Universiteit Amsterdam; Países BajosFil: Abels, Erik. Vrije Universiteit Amsterdam; Países BajosFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Kuijper, Lisan H.. Vrije Universiteit Amsterdam; Países BajosFil: de Miguel, Elena. Vrije Universiteit Amsterdam; Países BajosFil: Wouters, Valerie M. C. J.. Vrije Universiteit Amsterdam; Países BajosFil: Best, Myron G.. Vrije Universiteit Amsterdam; Países BajosFil: Rodriguez, Ernesto. Vrije Universiteit Amsterdam; Países BajosFil: Cornelissen, Lenneke A.M.. Vrije Universiteit Amsterdam; Países BajosFil: van Vliet, Sandra J.. Vrije Universiteit Amsterdam; Países BajosFil: Wesseling, Pieter. Vrije Universiteit Amsterdam; Países BajosFil: Breakefield, Xandra O.. Vrije Universiteit Amsterdam; Países BajosFil: Noske, David P.. Vrije Universiteit Amsterdam; Países BajosFil: Würdinger, Thomas. Harvard Medical School; Estados UnidosFil: Broekman, Marike L.D.. Harvard Medical School; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: van Kooyk, Yvette. Vrije Universiteit Amsterdam; Países BajosFil: Garcia Vallejo, Juan J.. Vrije Universiteit Amsterdam; Países BajosNational Academy of Sciences2020-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/143794Dusoswa, Sophie A.; Verhoeff, Jan; Abels, Erik; Mendez Huergo, Santiago Patricio; Croci Russo, Diego Omar; et al.; Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 7; 2-2020; 3693-37030027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1907921117info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/117/7/3693info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:16:43Zoai:ri.conicet.gov.ar:11336/143794instacron: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 10:16:43.33CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin
title Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin
spellingShingle Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin
Dusoswa, Sophie A.
GLIOBLASTOMA
IMMUNOSUPPRESSION
MACROPHAGE GALACTOSE LECTIN
MACROPHAGES
O-LINKED GLYCOSYLATION
title_short Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin
title_full Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin
title_fullStr Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin
title_full_unstemmed Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin
title_sort Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin
dc.creator.none.fl_str_mv Dusoswa, Sophie A.
Verhoeff, Jan
Abels, Erik
Mendez Huergo, Santiago Patricio
Croci Russo, Diego Omar
Kuijper, Lisan H.
de Miguel, Elena
Wouters, Valerie M. C. J.
Best, Myron G.
Rodriguez, Ernesto
Cornelissen, Lenneke A.M.
van Vliet, Sandra J.
Wesseling, Pieter
Breakefield, Xandra O.
Noske, David P.
Würdinger, Thomas
Broekman, Marike L.D.
Rabinovich, Gabriel Adrián
van Kooyk, Yvette
Garcia Vallejo, Juan J.
author Dusoswa, Sophie A.
author_facet Dusoswa, Sophie A.
Verhoeff, Jan
Abels, Erik
Mendez Huergo, Santiago Patricio
Croci Russo, Diego Omar
Kuijper, Lisan H.
de Miguel, Elena
Wouters, Valerie M. C. J.
Best, Myron G.
Rodriguez, Ernesto
Cornelissen, Lenneke A.M.
van Vliet, Sandra J.
Wesseling, Pieter
Breakefield, Xandra O.
Noske, David P.
Würdinger, Thomas
Broekman, Marike L.D.
Rabinovich, Gabriel Adrián
van Kooyk, Yvette
Garcia Vallejo, Juan J.
author_role author
author2 Verhoeff, Jan
Abels, Erik
Mendez Huergo, Santiago Patricio
Croci Russo, Diego Omar
Kuijper, Lisan H.
de Miguel, Elena
Wouters, Valerie M. C. J.
Best, Myron G.
Rodriguez, Ernesto
Cornelissen, Lenneke A.M.
van Vliet, Sandra J.
Wesseling, Pieter
Breakefield, Xandra O.
Noske, David P.
Würdinger, Thomas
Broekman, Marike L.D.
Rabinovich, Gabriel Adrián
van Kooyk, Yvette
Garcia Vallejo, Juan J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GLIOBLASTOMA
IMMUNOSUPPRESSION
MACROPHAGE GALACTOSE LECTIN
MACROPHAGES
O-LINKED GLYCOSYLATION
topic GLIOBLASTOMA
IMMUNOSUPPRESSION
MACROPHAGE GALACTOSE LECTIN
MACROPHAGES
O-LINKED GLYCOSYLATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), which are key mediators of immune suppression and resistance to immunotherapy. We and others demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans trigger inhibitory signaling in TAMs through glycan-binding receptors. We investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. We detected increased expression of both tumor-associated truncated O-linked glycans and their receptor, macrophage galactose-type lectin (MGL), on CD163+ TAMs in glioblastoma patient-derived tumor tissues. In an immunocompetent orthotopic glioma mouse model overexpressing truncated O-linked glycans (MGL ligands), high-dimensional mass cytometry revealed a wide heterogeneity of infiltrating myeloid cells with increased infiltration of PD-L1+ TAMs as well as distant alterations in the bone marrow (BM). Our results demonstrate that glioblastomas exploit cell surface O-linked glycans for local and distant immune modulation.
Fil: Dusoswa, Sophie A.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Verhoeff, Jan. Vrije Universiteit Amsterdam; Países Bajos
Fil: Abels, Erik. Vrije Universiteit Amsterdam; Países Bajos
Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Kuijper, Lisan H.. Vrije Universiteit Amsterdam; Países Bajos
Fil: de Miguel, Elena. Vrije Universiteit Amsterdam; Países Bajos
Fil: Wouters, Valerie M. C. J.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Best, Myron G.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Rodriguez, Ernesto. Vrije Universiteit Amsterdam; Países Bajos
Fil: Cornelissen, Lenneke A.M.. Vrije Universiteit Amsterdam; Países Bajos
Fil: van Vliet, Sandra J.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Wesseling, Pieter. Vrije Universiteit Amsterdam; Países Bajos
Fil: Breakefield, Xandra O.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Noske, David P.. Vrije Universiteit Amsterdam; Países Bajos
Fil: Würdinger, Thomas. Harvard Medical School; Estados Unidos
Fil: Broekman, Marike L.D.. Harvard Medical School; Estados Unidos
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: van Kooyk, Yvette. Vrije Universiteit Amsterdam; Países Bajos
Fil: Garcia Vallejo, Juan J.. Vrije Universiteit Amsterdam; Países Bajos
description Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), which are key mediators of immune suppression and resistance to immunotherapy. We and others demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans trigger inhibitory signaling in TAMs through glycan-binding receptors. We investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. We detected increased expression of both tumor-associated truncated O-linked glycans and their receptor, macrophage galactose-type lectin (MGL), on CD163+ TAMs in glioblastoma patient-derived tumor tissues. In an immunocompetent orthotopic glioma mouse model overexpressing truncated O-linked glycans (MGL ligands), high-dimensional mass cytometry revealed a wide heterogeneity of infiltrating myeloid cells with increased infiltration of PD-L1+ TAMs as well as distant alterations in the bone marrow (BM). Our results demonstrate that glioblastomas exploit cell surface O-linked glycans for local and distant immune modulation.
publishDate 2020
dc.date.none.fl_str_mv 2020-02
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/11336/143794
Dusoswa, Sophie A.; Verhoeff, Jan; Abels, Erik; Mendez Huergo, Santiago Patricio; Croci Russo, Diego Omar; et al.; Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 7; 2-2020; 3693-3703
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/143794
identifier_str_mv Dusoswa, Sophie A.; Verhoeff, Jan; Abels, Erik; Mendez Huergo, Santiago Patricio; Croci Russo, Diego Omar; et al.; Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 7; 2-2020; 3693-3703
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1907921117
info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/117/7/3693
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
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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
_version_ 1844614114574336000
score 13.069144

Publicaciones similares