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dc.contributor | Facultad de Veterinaria | es_ES |
dc.contributor.author | Rodríguez Barbosa, José Ignacio | |
dc.contributor.author | Azuma, Miyuki | |
dc.contributor.author | Zelinskyy, Gennadiy | |
dc.contributor.author | Pérez-Simón, José-Antonio | |
dc.contributor.author | Río González, María Luisa del | |
dc.contributor.other | Sanidad Animal | es_ES |
dc.date | 2020 | |
dc.date.accessioned | 2024-01-10T08:15:05Z | |
dc.date.available | 2024-01-10T08:15:05Z | |
dc.identifier.citation | Rodriguez-Barbosa, J. I., Azuma, M., Zelinskyy, G., Perez-Simon, J. A., & Del Rio, M. L. (2020). Critical role of PD-L1 expression on non-tumor cells rather than on tumor cells for effective anti-PD-L1 immunotherapy in a transplantable mouse hematopoietic tumor model. Cancer Immunology, Immunotherapy, 69(6), 1001-1014. | es_ES |
dc.identifier.issn | 0340-7004 | |
dc.identifier.uri | https://hdl.handle.net/10612/17569 | |
dc.description.abstract | [EN] The expression of PD-L1 on tumor cells or within the tumor microenvironment has been associated with good prognosis and sustained clinical responses in immunotherapeutic regimens based on PD-L1/PD-1/CD80 immune checkpoint blockade. To look into the current controversy in cancer immunotherapy of the relative importance of PD-L1 expression on tumor cells versus non-tumor cells of the tumor microenvironment, a hematological mouse tumor model was chosen. By combining a genetic CRISPR/Cas9 and immunotherapeutic approach and using a syngeneic hematopoietic transplantable tumor model (E.G7-cOVA tumor cells), we demonstrated that dual blockade of PD-L1 interaction with PD-1 and CD80 enhanced anti-tumor immune responses that either delayed tumor growth or led to its complete eradication. PD-L1 expression on non-tumor cells of the tumor microenvironment was required for the promotion of tumor immune escape and its blockade elicited potent anti-tumor responses to PD-L1 WT and to PD-L1-defcient tumor cells. PD-L1+ tumors implanted in PDL1-defcient mice exhibited delayed tumor growth independently of PD-L1 blockade. These fndings emphasize that PD-L1 expression on non-tumor cells plays a major role in this tumor model. These observations should turn our attention to the tumor microenvironment in hematological malignancies because of its unappreciated contribution to create a conditioned niche for the tumor to grow and evade the anti-tumor immune response. | es_ES |
dc.language | eng | es_ES |
dc.publisher | Springer | es_ES |
dc.subject | Veterinaria | es_ES |
dc.subject.other | PD-1 (programmed death-1) | es_ES |
dc.subject.other | PD-L1 (programmed death-ligand | es_ES |
dc.subject.other | Immune checkpoint blockade | es_ES |
dc.subject.other | Hematological malignancies | es_ES |
dc.subject.other | CRISPR/Cas9 | es_ES |
dc.title | Critical role of PD-L1 expression on non-tumor cells rather than on tumor cells for efective anti-PD-L1 immunotherapy in a transplantable mouse hematopoietic tumor model | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | doi.org/10.1007/s00262-020-02520-z | |
dc.description.peerreviewed | SI | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.essn | 1432-0851 | |
dc.journal.title | Cancer Immunology, Immunotherapy | es_ES |
dc.volume.number | 69 | es_ES |
dc.issue.number | 6 | es_ES |
dc.page.initial | 1001 | es_ES |
dc.page.final | 1014 | es_ES |
dc.type.hasVersion | info:eu-repo/semantics/acceptedVersion | es_ES |
dc.description.project | This work has been supported by Grant FIS PI# 1300029 (Fondo de Investigaciones Sanitarias, Ministry of Health, Spanish Government, and co-funded by European Union ERDF/ESF, “Investing in your future”), LE093U13 and Unit of Excellence Research UIC #012 (Department of Education of the Regional Government, Junta de Castilla y Leon) and Gerencia Regional de Salud (BIO/01/15) to JIRB. It was also funded by Miguel Servet National Grant (Health National Organization Research) CP12/03063, CPII17/00002 and FIS PI16/00002 (Instituto de Salud Carlos III and co-funded by European Union ERDF/ESF, “Investing in your future”), and Gerencia Regional de Salud GRS963/A/2014, GRS1142/A/2015 and GRS 1505/A/2017 to M.L.R.G. This work has been partially funded by the National Network CIBER-ONC (oncology research) CB16/12/00480. | es_ES |
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