CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma

BackgroundDiffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this s...

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Main Authors: Lourdes Hontecillas-Prieto, Daniel J. García-Domínguez, Natalia Palazón-Carrión, Alejandro Martín García-Sancho, Esteban Nogales-Fernández, Carlos Jiménez-Cortegana, María L. Sánchez-León, Silvia Silva-Romeiro, Rocío Flores-Campos, Fernando Carnicero-González, Eduardo Ríos-Herranz, Fátima de la Cruz-Vicente, Guillermo Rodríguez-García, Rubén Fernández-Álvarez, Natividad Martínez-Banaclocha, Josep Gumà-Padrò, José Gómez-Codina, Antonio Salar-Silvestre, Delvys Rodríguez-Abreu, Laura Gálvez-Carvajal, Jorge Labrador, María Guirado-Risueño, Mariano Provencio-Pulla, Margarita Sánchez-Beato, Lejeune Marylene, Tomás Álvaro-Naranjo, María Casanova-Espinosa, Antonio Rueda-Domínguez, Víctor Sánchez-Margalet, Luis de la Cruz-Merino
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293931/full
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author Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Daniel J. García-Domínguez
Daniel J. García-Domínguez
Natalia Palazón-Carrión
Natalia Palazón-Carrión
Alejandro Martín García-Sancho
Esteban Nogales-Fernández
Esteban Nogales-Fernández
Carlos Jiménez-Cortegana
María L. Sánchez-León
Silvia Silva-Romeiro
Rocío Flores-Campos
Fernando Carnicero-González
Eduardo Ríos-Herranz
Fátima de la Cruz-Vicente
Guillermo Rodríguez-García
Rubén Fernández-Álvarez
Natividad Martínez-Banaclocha
Josep Gumà-Padrò
José Gómez-Codina
Antonio Salar-Silvestre
Delvys Rodríguez-Abreu
Laura Gálvez-Carvajal
Jorge Labrador
María Guirado-Risueño
Mariano Provencio-Pulla
Margarita Sánchez-Beato
Lejeune Marylene
Tomás Álvaro-Naranjo
María Casanova-Espinosa
Antonio Rueda-Domínguez
Víctor Sánchez-Margalet
Víctor Sánchez-Margalet
Víctor Sánchez-Margalet
Luis de la Cruz-Merino
Luis de la Cruz-Merino
Luis de la Cruz-Merino
author_facet Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Daniel J. García-Domínguez
Daniel J. García-Domínguez
Natalia Palazón-Carrión
Natalia Palazón-Carrión
Alejandro Martín García-Sancho
Esteban Nogales-Fernández
Esteban Nogales-Fernández
Carlos Jiménez-Cortegana
María L. Sánchez-León
Silvia Silva-Romeiro
Rocío Flores-Campos
Fernando Carnicero-González
Eduardo Ríos-Herranz
Fátima de la Cruz-Vicente
Guillermo Rodríguez-García
Rubén Fernández-Álvarez
Natividad Martínez-Banaclocha
Josep Gumà-Padrò
José Gómez-Codina
Antonio Salar-Silvestre
Delvys Rodríguez-Abreu
Laura Gálvez-Carvajal
Jorge Labrador
María Guirado-Risueño
Mariano Provencio-Pulla
Margarita Sánchez-Beato
Lejeune Marylene
Tomás Álvaro-Naranjo
María Casanova-Espinosa
Antonio Rueda-Domínguez
Víctor Sánchez-Margalet
Víctor Sánchez-Margalet
Víctor Sánchez-Margalet
Luis de la Cruz-Merino
Luis de la Cruz-Merino
Luis de la Cruz-Merino
author_sort Lourdes Hontecillas-Prieto
collection DOAJ
description BackgroundDiffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients.Methods78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients.ResultsOur results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients.ConclusionCD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.
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spelling doaj.art-212d6baeaf2d4c8bb7bf0ab05ba407932024-02-26T11:08:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.12939311293931CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphomaLourdes Hontecillas-Prieto0Lourdes Hontecillas-Prieto1Lourdes Hontecillas-Prieto2Lourdes Hontecillas-Prieto3Daniel J. García-Domínguez4Daniel J. García-Domínguez5Natalia Palazón-Carrión6Natalia Palazón-Carrión7Alejandro Martín García-Sancho8Esteban Nogales-Fernández9Esteban Nogales-Fernández10Carlos Jiménez-Cortegana11María L. Sánchez-León12Silvia Silva-Romeiro13Rocío Flores-Campos14Fernando Carnicero-González15Eduardo Ríos-Herranz16Fátima de la Cruz-Vicente17Guillermo Rodríguez-García18Rubén Fernández-Álvarez19Natividad Martínez-Banaclocha20Josep Gumà-Padrò21José Gómez-Codina22Antonio Salar-Silvestre23Delvys Rodríguez-Abreu24Laura Gálvez-Carvajal25Jorge Labrador26María Guirado-Risueño27Mariano Provencio-Pulla28Margarita Sánchez-Beato29Lejeune Marylene30Tomás Álvaro-Naranjo31María Casanova-Espinosa32Antonio Rueda-Domínguez33Víctor Sánchez-Margalet34Víctor Sánchez-Margalet35Víctor Sánchez-Margalet36Luis de la Cruz-Merino37Luis de la Cruz-Merino38Luis de la Cruz-Merino39Clinical Biochemistry Service, Virgen Macarena University Hospital, University of Seville, Seville, SpainDepartment of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, SpainInstitute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, Seville, SpainClinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, SpainDepartment of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, SpainInstitute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, Seville, SpainClinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, SpainDepartment of Medicine, University of Seville, Seville, SpainDepartment of Hematology, Hospital Universitario de Salamanca, IBSAL, CIBERONC, University of Salamanca, Salamanca, SpainClinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, SpainDepartment of Medicine, University of Seville, Seville, SpainDepartment of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, SpainClinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, SpainClinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, SpainClinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, SpainDepartment of Hematology, Hospital San Pedro de Alcántara de Cáceres, Cáceres, SpainDepartment of Hematology, Hospital Universitario de Valme, Seville, SpainDepartment of Hematology, Hospital Universitario Virgen del Rocío, Seville, SpainDepartment of Hematology, Hospital Universitario Virgen del Rocío, Seville, Spain0Department of Hematology, Cabueñes Hospital, Gijón, Spain1Oncology Dept., Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain2Department of Clinical Oncology, Hospital Universitari Sant Joan de Reus URV, IISPV, Reus, Spain3Department of Clinical Oncology, Hospital Universitario La Fé, Valencia, Spain4Department of Hematology, Hospital del Mar, Barcelona, Spain5Department of Clinical Oncology, Hospital Universitario Insular, Las Palmas de Gran Canaria, Spain6Department of Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain7Department of Hematology, Research Unit, Hospital Universitario de Burgos, Burgos, Spain8Department of Clinical Oncology, Hospital General Universitario de Elche, Elche, Spain9Department of Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Facultad de Medicina, Universidad Autónoma de Madrid, IDIPHISA, Madrid, Spain0Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, CIBERONC, Madrid, Spain1Department of Pathology, Plataforma de Estudios Histológicos, Citológicos y de Digitalización, Hospital de Tortosa Verge de la Cinta, IISPV, URV, Tortosa, Tarragona, Spain2Department of Pathology, Hospital de Tortosa Verge de la Cinta, Catalan Institute of Health, Institut d’Investigació Sanitària Pere Virgili (IISPV), Tortosa, Tarragona, Spain3Department of Hematology/Clinical Oncology, Hospital Costa del Sol, Marbella, Spain3Department of Hematology/Clinical Oncology, Hospital Costa del Sol, Marbella, SpainClinical Biochemistry Service, Virgen Macarena University Hospital, University of Seville, Seville, SpainDepartment of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, SpainInstitute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, Seville, SpainInstitute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, Seville, SpainClinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, SpainDepartment of Medicine, University of Seville, Seville, SpainBackgroundDiffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients.Methods78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients.ResultsOur results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients.ConclusionCD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29. https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293931/fullDLBCLB cell lymphomarecurrent/refractory diseaseimmune systemnatural killerCD8+ NK
spellingShingle Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Lourdes Hontecillas-Prieto
Daniel J. García-Domínguez
Daniel J. García-Domínguez
Natalia Palazón-Carrión
Natalia Palazón-Carrión
Alejandro Martín García-Sancho
Esteban Nogales-Fernández
Esteban Nogales-Fernández
Carlos Jiménez-Cortegana
María L. Sánchez-León
Silvia Silva-Romeiro
Rocío Flores-Campos
Fernando Carnicero-González
Eduardo Ríos-Herranz
Fátima de la Cruz-Vicente
Guillermo Rodríguez-García
Rubén Fernández-Álvarez
Natividad Martínez-Banaclocha
Josep Gumà-Padrò
José Gómez-Codina
Antonio Salar-Silvestre
Delvys Rodríguez-Abreu
Laura Gálvez-Carvajal
Jorge Labrador
María Guirado-Risueño
Mariano Provencio-Pulla
Margarita Sánchez-Beato
Lejeune Marylene
Tomás Álvaro-Naranjo
María Casanova-Espinosa
Antonio Rueda-Domínguez
Víctor Sánchez-Margalet
Víctor Sánchez-Margalet
Víctor Sánchez-Margalet
Luis de la Cruz-Merino
Luis de la Cruz-Merino
Luis de la Cruz-Merino
CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma
Frontiers in Immunology
DLBCL
B cell lymphoma
recurrent/refractory disease
immune system
natural killer
CD8+ NK
title CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma
title_full CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma
title_fullStr CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma
title_full_unstemmed CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma
title_short CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma
title_sort cd8 nks as a potential biomarker of complete response and survival with lenalidomide plus r gdp in the r2 gdp gotel trial in recurrent refractory diffuse large b cell lymphoma
topic DLBCL
B cell lymphoma
recurrent/refractory disease
immune system
natural killer
CD8+ NK
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293931/full
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