Oleuropein-driven reprogramming of the myeloid cell compartment to sensitise tumours to PD-1/PD-L1 blockade strategies

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dc.contributor.authorBlanco, Ester
dc.contributor.authorSilva-Pilipich, Noelia
dc.contributor.authorBocanegra Gondán, Ana Isabel
dc.contributor.authorChocarro de Erauso, Luisa
dc.contributor.authorProcopio, Antonio
dc.contributor.authorAusín, Karina
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorFernández Rubio, Leticia
dc.contributor.authorRazquin, Nerea
dc.contributor.authorIgea, Ana
dc.contributor.authorGarnica, Maider
dc.contributor.authorEchaide Górriz, Míriam
dc.contributor.authorArasanz Esteban, Hugo
dc.contributor.authorVera García, Ruth
dc.contributor.authorEscors Murugarren, David
dc.contributor.authorSmerdou, Cristian
dc.contributor.authorKochan, Grazyna
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2024-04-08T17:40:52Z
dc.date.available2024-04-08T17:40:52Z
dc.date.issued2024
dc.date.updated2024-04-08T16:45:27Z
dc.description.abstractBackground: Previous studies have shown that functional systemic immunity is required for the efficacy of PD-1/PD-L1 blockade immunotherapies in cancer. Hence, systemic reprogramming of immunosuppressive dysfunctional myeloid cells could overcome resistance to cancer immunotherapy. Methods: Reprogramming of tumour-associated myeloid cells with oleuropein was studied by quantitative differential proteomics, phenotypic and functional assays in mice and lung cancer patients. Combinations of oleuropein and two different delivery methods of anti-PD-1 antibodies were tested in colorectal cancer tumour models and in immunotherapy-resistant lung cancer models. Results: Oleuropein treatment reprogrammed monocytic and granulocytic myeloid-derived suppressor cells, and tumour-associated macrophages towards differentiation of immunostimulatory subsets. Oleuropein regulated major differentiation programmes associated to immune modulation in myeloid cells, which potentiated T cell responses and PD-1 blockade. PD-1 antibodies were delivered by two different strategies, either systemically or expressed within tumours using a self-amplifying RNA vector. Combination anti-PD-1 therapies with oleuropein increased tumour infiltration by immunostimulatory dendritic cells in draining lymph nodes, leading to systemic antitumour T cell responses. Potent therapeutic activities were achieved in colon cancer and lung cancer models resistant to immunotherapies, even leading to complete tumour regression. Discussion: Oleuropein significantly improves the outcome of PD-1/PD-L1 blockade immunotherapy strategies by reprogramming myeloid cells.en
dc.description.sponsorshipThis work was supported by the following grants: Instituto Salud Carlos III financed with FEDER Funds PI20/00415 (“A way to make Europe”), Gobierno de Navarra, Departamento de Salud (GN2022/21), and Fundación Intheos. NS-P received a “Ayudas predoctorales de investigación biomédica AC” fellowship granted to CS, the Spanish Association against Cancer (AECC), PROYE16001ESCO, IDEAS211016AJON to (DE, GK, RV); LC received a studentship from Instituto de Salud Carlos (III), co-financed by FEDER funds (Contratos PFIS, contratos predoctorales de formación en investigación en salud, FI21/00080); further financing was obtained from Instituto de Salud Carlos III (ISCIII)-FEDER Project grants FIS PI20/00010, FIS PI20/00419, FIS PI23/00196 (DE, GK); Biomedicine Project Grant from the Department of Health of the Government of Navarre-FEDER funds (BMED 050-2019, 51-2021) granted to (DE); Project grant ARMUNE (0011-1411-2023-000111) financed by Departamento de Desarrollo Económico y Empresarial (Government of Navarra).en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBlanco, E., Silva-Pilipich, N., Bocanegra, A., Chocarro, L., Procopio, A., Ausín, K., Fernandez-Irigoyen, J., Fernández, L., Razquin, N., Igea, A., Garnica, M., Echaide, M., Arasanz, H., Vera, R., Escors, D., Smerdou, C., & Kochan, G. (2024). Oleuropein-driven reprogramming of the myeloid cell compartment to sensitise tumours to PD-1/PD-L1 blockade strategies. British Journal of Cancer, 130(5), 869-879. https://doi.org/10.1038/s41416-023-02561-yen
dc.identifier.doi10.1038/s41416-023-02561-y
dc.identifier.issn0007-0920
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/47820
dc.language.isoengen
dc.publisherSpringer Natureen
dc.relation.ispartofBritish Journal of Cancer (2024), 130, 869–879en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00415/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00010/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00419/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII//PI23%2F00196
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//GN2022%2F21
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//050-2019
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//51-2021
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//0011-1411-2023-000111
dc.relation.publisherversionhttps://doi.org/10.1038/s41416-023-02561-y
dc.rights© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectPD-1/PD-L1 blockade immunotherapiesen
dc.subjectMyeloid cellsen
dc.subjectOleuropeinen
dc.subjectColon canceren
dc.subjectLung canceren
dc.titleOleuropein-driven reprogramming of the myeloid cell compartment to sensitise tumours to PD-1/PD-L1 blockade strategiesen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationfe5c362e-3c0c-4edb-aa2e-0de27c815ad2
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublication.latestForDiscoveryfe5c362e-3c0c-4edb-aa2e-0de27c815ad2

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