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Activating KIRs on Educated NK Cells Support Downregulation of CD226 and Inefficient Tumor Immunosurveillance

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dc.contributor.authorGuillamón, Concepción F.
dc.contributor.authorMartínez Sánchez, María V.
dc.contributor.authorCampillo, José A.
dc.contributor.authorServer Pastor, Gerardo
dc.contributor.authorMartínez García, Jerónimo
dc.contributor.authorMartínez Escribano, Jorge
dc.contributor.authorTorroba, Amparo
dc.contributor.authorFerri, Belén
dc.contributor.authorAbellán, Daniel J.
dc.contributor.authorLópez Álvarez, María R.
dc.contributor.authorMoya Quiles, María R.
dc.contributor.authorMuro, Manuel
dc.contributor.authorMinguela, Alfredo
dc.contributor.authorGimeno Arias, Lourdes
dc.contributor.authorLegaz Pérez, Isabel
dc.contributor.departmentCiencias Sociosanitarias
dc.date.accessioned2024-07-11T11:31:59Z
dc.date.available2024-07-11T11:31:59Z
dc.date.issued2019-08-01
dc.description© 2019 American Association for Cancer Research. This document is the Published version of a Published Work that appeared in final form in Cancer Immunology Research. To access the final edited and published work see https://doi.org/10.1158/2326-6066.CIR-18-0847
dc.description.abstractTherapies using NK cells (NKc) expanded/activated ex vivo or stimulated in vivo with new immunostimulatory agents offer alternative opportunities for patients with recurrent/refractory tumors, but relevant biomarkers to guide the selection of patients are required for optimum results. Overall survival of 249 solid cancer patients was evaluated in relation to the genetics and/or the expression on peripheral blood NKcs of inhibitory and activating killer-cell immunoglobulin-like receptors (iKIR and aKIR, respectively), HLA class I ligands, CD226 (also known as DNAM-1), and NKG2A. Compared with patients with higher expression, patients with low expression of CD226 on total NKcs showed shorter mean overall survival (60.7 vs. 98.0 months, P < 0.001), which was further reduced in presence of telomeric aKIRs (KIR2DS1-DS5 and/or KIR3DS1, 31.6 vs. 96.8 months, P < 0.001). KIR2DL2/S2+, KIR3DL1+, KIR2DL1+, and KIR2DL3+ NKc subsets in the presence of their cognate ligands primarily contributed to shortening patients’ overall survival by increasing the sensitivity to CD226 downmodulation in aKIR-rich telomeric genotypes. In patients with high tumor burden who died during the follow-up period, aKIR-rich telomeric genotypes were associated with: (i) specific downmodulation of CD226 on educated NKcs but not on CD8+ T cells or uneducated NKcs, (ii) lower expression of CD226 and higher expression of NKG2A on aKIR+ NKcs, and (iii) lower numbers of total CD56dim NKcs. The reduced expression of CD226 on NKcs with aKIR-rich genotypes may be a biomarker indicative of NKc hyporesponsiveness in patients that could benefit from new NKc immune-stimulatory therapies.es
dc.formatapplication/pdfes
dc.format.extent11es
dc.identifier.citationCancer Immunology Research, 2019, Vol. 7 (8), pp. 1307–1317
dc.identifier.doihttps://doi.org/10.1158/2326-6066.CIR-18-0847
dc.identifier.issnPrint: 2326-6066
dc.identifier.issnElectronic: 2326-6074
dc.identifier.urihttp://hdl.handle.net/10201/142997
dc.languageenges
dc.publisherAmerican Association for Cancer Research
dc.relationThis work was funded by MINECO - Instituto de Salud Carlos III (PI1302297) and Fundación Séneca, Agencia de Ciencia y Tecnología, Región de Murcia (20812/PI/18). C.F. Guillamón was funded by the Fundación para el estudio y el desarrollo de la inmunogenética en Murcia (FEYDIM). M.V. Martínez-Sánchez was funded by the Asociación Pablo Ugarte (APU).es
dc.relation.publisherversionhttps://aacrjournals.org/cancerimmunolres/article/7/8/1307/469581/Activating-KIRs-on-Educated-NK-Cells-Support
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.titleActivating KIRs on Educated NK Cells Support Downregulation of CD226 and Inefficient Tumor Immunosurveillancees
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublicationa0170301-b64f-46f8-810a-ff18c9bf0a5f
relation.isAuthorOfPublicationb83b4b59-2d61-40f0-9108-5c6a6d158295
relation.isAuthorOfPublication.latestForDiscoverya0170301-b64f-46f8-810a-ff18c9bf0a5f
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