Cargando…

Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial

BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumor...

Descripción completa

Detalles Bibliográficos
Autores principales: Jiménez-Cortegana, Carlos, Palazón-Carrión, Natalia, Martin Garcia-Sancho, Alejandro, Nogales-Fernandez, Esteban, Carnicero-González, Fernando, Ríos-Herranz, Eduardo, de la Cruz-Vicente, Fatima, Rodríguez-García, Guillermo, Fernández-Álvarez, Rubén, Rueda Dominguez, Antonio, Casanova-Espinosa, Maria, Martínez-Banaclocha, Natividad, Gumà-Padrò, Josep, Gómez-Codina, José, Labrador, Jorge, Salar-Silvestre, Antonio, Rodriguez-Abreu, Delvys, Galvez-Carvajal, Laura, Provencio, Mariano, Sánchez-Beato, Margarita, Guirado-Risueño, María, Espejo-García, Pablo, Lejeune, Marylene, Álvaro, Tomás, Sánchez-Margalet, Victor, de la Cruz-Merino, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728348/
https://www.ncbi.nlm.nih.gov/pubmed/34158317
http://dx.doi.org/10.1136/jitc-2020-002323
_version_ 1784626714252410880
author Jiménez-Cortegana, Carlos
Palazón-Carrión, Natalia
Martin Garcia-Sancho, Alejandro
Nogales-Fernandez, Esteban
Carnicero-González, Fernando
Ríos-Herranz, Eduardo
de la Cruz-Vicente, Fatima
Rodríguez-García, Guillermo
Fernández-Álvarez, Rubén
Rueda Dominguez, Antonio
Casanova-Espinosa, Maria
Martínez-Banaclocha, Natividad
Gumà-Padrò, Josep
Gómez-Codina, José
Labrador, Jorge
Salar-Silvestre, Antonio
Rodriguez-Abreu, Delvys
Galvez-Carvajal, Laura
Provencio, Mariano
Sánchez-Beato, Margarita
Guirado-Risueño, María
Espejo-García, Pablo
Lejeune, Marylene
Álvaro, Tomás
Sánchez-Margalet, Victor
de la Cruz-Merino, Luis
author_facet Jiménez-Cortegana, Carlos
Palazón-Carrión, Natalia
Martin Garcia-Sancho, Alejandro
Nogales-Fernandez, Esteban
Carnicero-González, Fernando
Ríos-Herranz, Eduardo
de la Cruz-Vicente, Fatima
Rodríguez-García, Guillermo
Fernández-Álvarez, Rubén
Rueda Dominguez, Antonio
Casanova-Espinosa, Maria
Martínez-Banaclocha, Natividad
Gumà-Padrò, Josep
Gómez-Codina, José
Labrador, Jorge
Salar-Silvestre, Antonio
Rodriguez-Abreu, Delvys
Galvez-Carvajal, Laura
Provencio, Mariano
Sánchez-Beato, Margarita
Guirado-Risueño, María
Espejo-García, Pablo
Lejeune, Marylene
Álvaro, Tomás
Sánchez-Margalet, Victor
de la Cruz-Merino, Luis
author_sort Jiménez-Cortegana, Carlos
collection PubMed
description BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. METHODS: Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. RESULTS: In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. CONCLUSIONS: In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.
format Online
Article
Text
id pubmed-8728348
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-87283482022-01-18 Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial Jiménez-Cortegana, Carlos Palazón-Carrión, Natalia Martin Garcia-Sancho, Alejandro Nogales-Fernandez, Esteban Carnicero-González, Fernando Ríos-Herranz, Eduardo de la Cruz-Vicente, Fatima Rodríguez-García, Guillermo Fernández-Álvarez, Rubén Rueda Dominguez, Antonio Casanova-Espinosa, Maria Martínez-Banaclocha, Natividad Gumà-Padrò, Josep Gómez-Codina, José Labrador, Jorge Salar-Silvestre, Antonio Rodriguez-Abreu, Delvys Galvez-Carvajal, Laura Provencio, Mariano Sánchez-Beato, Margarita Guirado-Risueño, María Espejo-García, Pablo Lejeune, Marylene Álvaro, Tomás Sánchez-Margalet, Victor de la Cruz-Merino, Luis J Immunother Cancer Immunotherapy Biomarkers BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. METHODS: Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. RESULTS: In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. CONCLUSIONS: In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL. BMJ Publishing Group 2021-06-21 /pmc/articles/PMC8728348/ /pubmed/34158317 http://dx.doi.org/10.1136/jitc-2020-002323 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Immunotherapy Biomarkers
Jiménez-Cortegana, Carlos
Palazón-Carrión, Natalia
Martin Garcia-Sancho, Alejandro
Nogales-Fernandez, Esteban
Carnicero-González, Fernando
Ríos-Herranz, Eduardo
de la Cruz-Vicente, Fatima
Rodríguez-García, Guillermo
Fernández-Álvarez, Rubén
Rueda Dominguez, Antonio
Casanova-Espinosa, Maria
Martínez-Banaclocha, Natividad
Gumà-Padrò, Josep
Gómez-Codina, José
Labrador, Jorge
Salar-Silvestre, Antonio
Rodriguez-Abreu, Delvys
Galvez-Carvajal, Laura
Provencio, Mariano
Sánchez-Beato, Margarita
Guirado-Risueño, María
Espejo-García, Pablo
Lejeune, Marylene
Álvaro, Tomás
Sánchez-Margalet, Victor
de la Cruz-Merino, Luis
Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial
title Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial
title_full Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial
title_fullStr Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial
title_full_unstemmed Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial
title_short Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial
title_sort circulating myeloid-derived suppressor cells and regulatory t cells as immunological biomarkers in refractory/relapsed diffuse large b-cell lymphoma: translational results from the r2-gdp-gotel trial
topic Immunotherapy Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728348/
https://www.ncbi.nlm.nih.gov/pubmed/34158317
http://dx.doi.org/10.1136/jitc-2020-002323
work_keys_str_mv AT jimenezcorteganacarlos circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT palazoncarrionnatalia circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT martingarciasanchoalejandro circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT nogalesfernandezesteban circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT carnicerogonzalezfernando circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT riosherranzeduardo circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT delacruzvicentefatima circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT rodriguezgarciaguillermo circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT fernandezalvarezruben circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT ruedadominguezantonio circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT casanovaespinosamaria circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT martinezbanaclochanatividad circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT gumapadrojosep circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT gomezcodinajose circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT labradorjorge circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT salarsilvestreantonio circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT rodriguezabreudelvys circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT galvezcarvajallaura circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT provenciomariano circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT sanchezbeatomargarita circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT guiradorisuenomaria circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT espejogarciapablo circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT lejeunemarylene circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT alvarotomas circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT sanchezmargaletvictor circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial
AT delacruzmerinoluis circulatingmyeloidderivedsuppressorcellsandregulatorytcellsasimmunologicalbiomarkersinrefractoryrelapseddiffuselargebcelllymphomatranslationalresultsfromther2gdpgoteltrial