NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma
Background: Activating and inhibitory receptors of natural killer (NK) cells such as NKp, NKG2, or CLEC are highly relevant to cold tumors including glioblastoma (GBM). Here, we aimed to characterize the expression of these receptors in GBM to gain insight into their potential role as modulators of...
| Autores: | , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/25097 |
| Acceso en línea: | https://hdl.handle.net/20.500.12105/25097 |
| Access Level: | acceso abierto |
| Palabra clave: | Central Nervous System Cancer Immune Checkpoint Inhibitor Macrophage NK Cell Lectin-Like Receptor Subfamily K Tumor microenvironment - TME Animals Brain Neoplasms Cell Line, Tumor Female Glioblastoma Humans Immunotherapy Killer Cells, Natural Mice NK Cell Lectin-Like Receptor Subfamily C Tumor Microenvironment |
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España |
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| dc.title.none.fl_str_mv |
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma |
| title |
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma |
| spellingShingle |
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma Dios Huerta, Olaya de Central Nervous System Cancer Immune Checkpoint Inhibitor Macrophage NK Cell Lectin-Like Receptor Subfamily K Tumor microenvironment - TME Animals Brain Neoplasms Cell Line, Tumor Female Glioblastoma Humans Immunotherapy Killer Cells, Natural Mice NK Cell Lectin-Like Receptor Subfamily C Tumor Microenvironment |
| title_short |
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma |
| title_full |
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma |
| title_fullStr |
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma |
| title_full_unstemmed |
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma |
| title_sort |
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma |
| dc.creator.none.fl_str_mv |
Dios Huerta, Olaya de Ramírez-González, María A Gómez-Soria, Irene Segura-Collar, Berta Manosalva, Juliana Megías, Diego de Andrea, Carlos E Fernández-Rubio, Leticia Hernández-Laín, Aurelio Sepúlveda-Sánchez, Juan Manuel Rodriguez-Ruiz, Maria E Pérez-Núñez, Ángel Wainwright, Derek A Gargini, Ricardo Sánchez-Gómez, Pilar |
| author |
Dios Huerta, Olaya de |
| author_facet |
Dios Huerta, Olaya de Ramírez-González, María A Gómez-Soria, Irene Segura-Collar, Berta Manosalva, Juliana Megías, Diego de Andrea, Carlos E Fernández-Rubio, Leticia Hernández-Laín, Aurelio Sepúlveda-Sánchez, Juan Manuel Rodriguez-Ruiz, Maria E Pérez-Núñez, Ángel Wainwright, Derek A Gargini, Ricardo Sánchez-Gómez, Pilar |
| author_role |
author |
| author2 |
Ramírez-González, María A Gómez-Soria, Irene Segura-Collar, Berta Manosalva, Juliana Megías, Diego de Andrea, Carlos E Fernández-Rubio, Leticia Hernández-Laín, Aurelio Sepúlveda-Sánchez, Juan Manuel Rodriguez-Ruiz, Maria E Pérez-Núñez, Ángel Wainwright, Derek A Gargini, Ricardo Sánchez-Gómez, Pilar |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia, Innovación y Universidades (España) Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) Instituto de Salud Carlos III National Institutes of Health (Estados Unidos) Cancer Research UK (Reino Unido) American Cancer Society Asociación Española Contra el Cáncer Brain Tumor Association (ABTA) |
| dc.subject.none.fl_str_mv |
Central Nervous System Cancer Immune Checkpoint Inhibitor Macrophage NK Cell Lectin-Like Receptor Subfamily K Tumor microenvironment - TME Animals Brain Neoplasms Cell Line, Tumor Female Glioblastoma Humans Immunotherapy Killer Cells, Natural Mice NK Cell Lectin-Like Receptor Subfamily C Tumor Microenvironment |
| topic |
Central Nervous System Cancer Immune Checkpoint Inhibitor Macrophage NK Cell Lectin-Like Receptor Subfamily K Tumor microenvironment - TME Animals Brain Neoplasms Cell Line, Tumor Female Glioblastoma Humans Immunotherapy Killer Cells, Natural Mice NK Cell Lectin-Like Receptor Subfamily C Tumor Microenvironment |
| description |
Background: Activating and inhibitory receptors of natural killer (NK) cells such as NKp, NKG2, or CLEC are highly relevant to cold tumors including glioblastoma (GBM). Here, we aimed to characterize the expression of these receptors in GBM to gain insight into their potential role as modulators of the intratumoral microenvironment. Methods: We performed a transcriptomic analysis of several NK receptors with a focus on the activating receptor encoded by KLRC2, NKG2C, among bulk and single-cell RNA sequencing GBM data sets. We also evaluated the effects of KLRC2-overexpressing GL261 cells in mice treated with or without programmed cell death protein-1 (PD-1) monoclonal antibody (mAb). Finally, we analyzed samples from two clinical trials evaluating PD-1 mAb effects in patients with GBM to determine the potential of NKG2C to serve as a biomarker of response. Results: We observed significant expression of several inhibitory NK receptors on GBM-infiltrating NK and T cells, which contrasts with the strong expression of KLRC2 on tumor cells, mainly at the infiltrative margin. Neoplastic KLRC2 expression was associated with a reduction in the number of myeloid-derived suppressor cells and with a higher level of tumor-resident lymphocytes. A stronger antitumor activity after PD-1 mAb treatment was observed in NKG2Chigh-expressing tumors both in mouse models and patients with GBM whereas the expression of inhibitory NK receptors showed an inverse association. Conclusions: This study explored the role of neoplastic NKG2C/KLRC2 expression in shaping the immune profile of GBM and suggests that it is a predictive biomarker for positive responses to immune checkpoint inhibitor treatment in patients with GBM. Future studies could further validate this finding in prospective trials. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024-10-14 2024 2024-08-30 2024 2024-08-30 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.12105/25097 |
| url |
https://hdl.handle.net/20.500.12105/25097 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI20%2F00434 INMUNOTERAPIA INTRATUMORAL BASADA EN AGONISTAS TLR3 COMO POTENCIADOR DE LOS EFECTOS LOCALES Y SISTEMICOS DE LA RADIOTERAPIA ES RTC2019-006860-1 Not available Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI21%2F01406 NUEVAS ESTRATEGIAS CONTRA LAS RESISTENCIAS TERAPEUTICAS DE LOS GLIOMAS CENTRADAS EN EL MICROAMBIENTE TUMORAL Y SUS REGULADORES. Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023 PI22%2F01171 Reprogramación epigenómica del microambiente tumoral para eliminar los oncogenes que promueven al glioma Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI21%2F01168 CARACTERIZACION DEL AREA PERITUMORAL DE LOS GLIOBLASTOMAS: QUEMANDO LOS PUENTES HACIA LA PROGRESION ES PI21CIII 00002 ES TED2021-132318B-I00 Not available ES P2022 BMD-7344 ES CD21 00080 ES CD22CIII 00001 ES CP21 00116 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ |
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openAccess |
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application/pdf application/vnd.openxmlformats-officedocument.spreadsheetml.sheet application/vnd.openxmlformats-officedocument.spreadsheetml.sheet application/pdf application/vnd.openxmlformats-officedocument.spreadsheetml.sheet application/pdf application/pdf application/pdf application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
BMJ Publishing Group |
| publisher.none.fl_str_mv |
BMJ Publishing Group |
| dc.source.none.fl_str_mv |
reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII) |
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Instituto de Salud Carlos III (ISCIII) |
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Repisalud |
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Repisalud |
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1869403995352596480 |
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NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastomaDios Huerta, Olaya deRamírez-González, María AGómez-Soria, IreneSegura-Collar, BertaManosalva, JulianaMegías, Diegode Andrea, Carlos EFernández-Rubio, LeticiaHernández-Laín, AurelioSepúlveda-Sánchez, Juan ManuelRodriguez-Ruiz, Maria EPérez-Núñez, ÁngelWainwright, Derek AGargini, RicardoSánchez-Gómez, PilarCentral Nervous System CancerImmune Checkpoint InhibitorMacrophageNK Cell Lectin-Like Receptor Subfamily KTumor microenvironment - TMEAnimalsBrain NeoplasmsCell Line, TumorFemaleGlioblastomaHumansImmunotherapyKiller Cells, NaturalMiceNK Cell Lectin-Like Receptor Subfamily CTumor MicroenvironmentBackground: Activating and inhibitory receptors of natural killer (NK) cells such as NKp, NKG2, or CLEC are highly relevant to cold tumors including glioblastoma (GBM). Here, we aimed to characterize the expression of these receptors in GBM to gain insight into their potential role as modulators of the intratumoral microenvironment. Methods: We performed a transcriptomic analysis of several NK receptors with a focus on the activating receptor encoded by KLRC2, NKG2C, among bulk and single-cell RNA sequencing GBM data sets. We also evaluated the effects of KLRC2-overexpressing GL261 cells in mice treated with or without programmed cell death protein-1 (PD-1) monoclonal antibody (mAb). Finally, we analyzed samples from two clinical trials evaluating PD-1 mAb effects in patients with GBM to determine the potential of NKG2C to serve as a biomarker of response. Results: We observed significant expression of several inhibitory NK receptors on GBM-infiltrating NK and T cells, which contrasts with the strong expression of KLRC2 on tumor cells, mainly at the infiltrative margin. Neoplastic KLRC2 expression was associated with a reduction in the number of myeloid-derived suppressor cells and with a higher level of tumor-resident lymphocytes. A stronger antitumor activity after PD-1 mAb treatment was observed in NKG2Chigh-expressing tumors both in mouse models and patients with GBM whereas the expression of inhibitory NK receptors showed an inverse association. Conclusions: This study explored the role of neoplastic NKG2C/KLRC2 expression in shaping the immune profile of GBM and suggests that it is a predictive biomarker for positive responses to immune checkpoint inhibitor treatment in patients with GBM. Future studies could further validate this finding in prospective trials.BMJ Publishing GroupMinisterio de Ciencia, Innovación y Universidades (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Instituto de Salud Carlos IIINational Institutes of Health (Estados Unidos)Cancer Research UK (Reino Unido)American Cancer SocietyAsociación Española Contra el CáncerBrain Tumor Association (ABTA)20242024-10-1420242024-08-3020242024-08-30research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheetapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheetapplication/pdfapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheetapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/20.500.12105/25097reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengInstituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI20%2F00434 INMUNOTERAPIA INTRATUMORAL BASADA EN AGONISTAS TLR3 COMO POTENCIADOR DE LOS EFECTOS LOCALES Y SISTEMICOS DE LA RADIOTERAPIAES RTC2019-006860-1 Not availableInstituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI21%2F01406 NUEVAS ESTRATEGIAS CONTRA LAS RESISTENCIAS TERAPEUTICAS DE LOS GLIOMAS CENTRADAS EN EL MICROAMBIENTE TUMORAL Y SUS REGULADORES.Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023 PI22%2F01171 Reprogramación epigenómica del microambiente tumoral para eliminar los oncogenes que promueven al gliomaInstituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI21%2F01168 CARACTERIZACION DEL AREA PERITUMORAL DE LOS GLIOBLASTOMAS: QUEMANDO LOS PUENTES HACIA LA PROGRESIONES PI21CIII 00002ES TED2021-132318B-I00 Not availableES P2022 BMD-7344ES CD21 00080ES CD22CIII 00001ES CP21 00116open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/250972026-06-12T12:43:37Z |
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