A proteomic atlas of lineage and cancer-polarized expression modules in myeloid cells modeling immunosuppressive tumor-infiltrating subsets

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dc.contributor.authorBlanco, Ester
dc.contributor.authorIbañez Vea, María
dc.contributor.authorHernández, Carlos
dc.contributor.authorDrici, Lylia
dc.contributor.authorMartínez de Morentin Iribarren, Xabier
dc.contributor.authorGato Cañas, María
dc.contributor.authorAusín, Karina
dc.contributor.authorBocanegra Gondán, Ana Isabel
dc.contributor.authorZuazo Ibarra, Miren
dc.contributor.authorChocarro de Erauso, Luisa
dc.contributor.authorArasanz Esteban, Hugo
dc.contributor.authorFernández Hinojal, Gonzalo
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSmerdou, Cristian
dc.contributor.authorGarnica, Maider
dc.contributor.authorEchaide Górriz, Míriam
dc.contributor.authorFernández Rubio, Leticia
dc.contributor.authorMorente Sancho, Pilar
dc.contributor.authorRamos-Castellanos, Pablo
dc.contributor.authorLlopiz, Diana
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorLarsen, Martin R.
dc.contributor.authorEscors Murugarren, David
dc.contributor.authorKochan, Grazyna
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.departmentInstitute for Multidisciplinary Research in Applied Biology - IMABen
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2022-01-11T09:29:24Z
dc.date.available2022-01-11T09:29:24Z
dc.date.issued2021
dc.description.abstractMonocytic and granulocytic myeloid-derived suppressor cells together with tumor-infiltrating macrophages constitute the main tumor-infiltrating immunosuppressive myeloid populations. Due to the phenotypic resemblance to conventional myeloid cells, their identification and purification from within the tumors is technically difficult and makes their study a challenge. We differentiated myeloid cells modeling the three main tumor-infiltrating types together with uncommitted macrophages, using ex vivo differentiation methods resembling the tumor microenvironment. The phenotype and proteome of these cells was compared to identify linage-dependent relationships and cancer-specific interactome expression modules. The relationships between monocytic MDSCs and TAMs, monocytic MDSCs and granulocytic MDSCs, and hierarchical relationships of expression networks and transcription factors due to lineage and cancer polarization were mapped. Highly purified immunosuppressive myeloid cell populations that model tumor-infiltrating counterparts were systematically analyzed by quantitative proteomics. Full functional interactome maps have been generated to characterize at high resolution the relationships between the three main myeloid tumor-infiltrating cell types. Our data highlights the biological processes related to each cell type, and uncover novel shared and differential molecular targets. Moreover, the high numbers and fidelity of ex vivo-generated subsets to their natu-ral tumor-shaped counterparts enable their use for validation of new treatments in high-throughput experiments.en
dc.description.sponsorshipThe Oncoimmunology Group is funded by the Spanish Association against Cancer (AECC, PROYE16001ESCO); Instituto de Salud Carlos III (ISCIII)-FEDER Project Grants FIS PI17/02119, FIS PI20/00010; COV20/00000, and TRANSPOCART ICI19/00069; Biomedicine Project Grant from the Department of Health of the Government of Navarre-FEDER funds (BMED 050-2019); strategic projects from the Department of Industry, Government of Navarre (AGATA, Ref. 0011-1411-2020-000013; LINTERNA, Ref. 0011-1411-2020-000033; DESCARTHES, 0011-1411-2019-000058); European Project Horizon 2020 Improved Vaccination for Older Adults (ISOLDA; ID: 848166).es
dc.format.extent21 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.3390/jpm11060542
dc.identifier.issn2075-4426
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/41692
dc.language.isoengen
dc.publisherMDPI
dc.relation.ispartofJournal of Personalized Medicine, 11 (6)
dc.relation.projectIDinfo:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/848166/
dc.relation.publisherversionhttp://doi.org/10.3390/jpm11060542
dc.rights© 2021 by the authors. Creative Commons Attributionen
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCanceren
dc.subjectMyeloid-derived suppressor cellsen
dc.subjectTumor-infiltrating macrophagesen
dc.titleA proteomic atlas of lineage and cancer-polarized expression modules in myeloid cells modeling immunosuppressive tumor-infiltrating subsetsen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationf96114c2-9fc5-4886-ab9a-4804f14aa9c6
relation.isAuthorOfPublication193d800d-c38c-4627-b9d8-d29435d8214c
relation.isAuthorOfPublicationfe5c362e-3c0c-4edb-aa2e-0de27c815ad2
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication.latestForDiscoveryf96114c2-9fc5-4886-ab9a-4804f14aa9c6

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