Articles producció científica> Ciències Mèdiques Bàsiques

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

  • Identification data

    Identifier: imarina:9220633
    Authors:
    Jimenez-Cortegana, CarlosPalazon-Carrion, NataliaGarcia-Sancho, Alejandro MartinNogales-Fernandez, EstebanCarnicero-Gonzalez, FernandoRios-Herranz, Eduardode la Cruz-Vicente, FatimaRodriguez-Garcia, GuillermoFernandez-Alvarez, RubenDominguez, Antonio RuedaCasanova-Espinosa, MariaMartinez-Banaclocha, NatividadGuma-Padro, JosepGomez-Codina, JoseLabrador, JorgeSalar-Silvestre, AntonioRodriguez-Abreu, DelvysGalvez-Carvajal, LauraProvencio, MarianoSanchez-Beato, MargaritaGuirado-Risueno, MariaEspejo-Garcia, PabloLejeune, MaryleneAlvaro, TomasSanchez-Margalet, Victorde la Cruz-Merino, Luis
    Abstract:
    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 ove
  • Others:

    Author, as appears in the article.: Jimenez-Cortegana, Carlos; Palazon-Carrion, Natalia; Garcia-Sancho, Alejandro Martin; Nogales-Fernandez, Esteban; Carnicero-Gonzalez, Fernando; Rios-Herranz, Eduardo; de la Cruz-Vicente, Fatima; Rodriguez-Garcia, Guillermo; Fernandez-Alvarez, Ruben; Dominguez, Antonio Rueda; Casanova-Espinosa, Maria; Martinez-Banaclocha, Natividad; Guma-Padro, Josep; Gomez-Codina, Jose; Labrador, Jorge; Salar-Silvestre, Antonio; Rodriguez-Abreu, Delvys; Galvez-Carvajal, Laura; Provencio, Mariano; Sanchez-Beato, Margarita; Guirado-Risueno, Maria; Espejo-Garcia, Pablo; Lejeune, Marylene; Alvaro, Tomas; Sanchez-Margalet, Victor; de la Cruz-Merino, Luis
    Department: Ciències Mèdiques Bàsiques
    URV's Author/s: Gumà Padró, José / Lejeune, Marylène Marie
    Keywords: Tumor Treatment outcome T-lymphocytes, regulatory Survival analysis Programmed cell death 1 receptor Phase-ii Pdcd1 protein, human Myeloid-derived suppressor cells Middle aged Male Lymphoma, large b-cell, diffuse Immunotherapy Immunomodulation Immunity Humans Gene expression regulation, neoplastic Female Clinical trials as topic Cellular Case-control studies Biomarkers, tumor Biomarkers Antineoplastic combined chemotherapy protocols Aged, 80 and over Aged Adult tumor rituximab myeloid-derived suppressor cells multicenter lenalidomide immunotherapy immunomodulation immunity gemcitabine expansion combination cellular breast-cancer blood association
    Abstract: 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.
    Thematic Areas: Pharmacology Oncology Molecular medicine Medicina i Immunology and allergy Immunology Cancer research
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: marylenemarie.lejeune@urv.cat jose.guma@urv.cat
    Author identifier: 0000-0001-8441-9404 0000-0001-7541-9832
    Record's date: 2024-10-12
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://jitc.bmj.com/content/9/6/e002323
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Journal For Immunotherapy Of Cancer. 9 (6): e002323-
    APA: Jimenez-Cortegana, Carlos; Palazon-Carrion, Natalia; Garcia-Sancho, Alejandro Martin; Nogales-Fernandez, Esteban; Carnicero-Gonzalez, Fernando; Rios-H (2021). 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. Journal For Immunotherapy Of Cancer, 9(6), e002323-. DOI: 10.1136/jitc-2020-002323
    Article's DOI: 10.1136/jitc-2020-002323
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2021
    Publication Type: Journal Publications
  • Keywords:

    Cancer Research,Immunology,Immunology and Allergy,Molecular Medicine,Oncology,Pharmacology
    Tumor
    Treatment outcome
    T-lymphocytes, regulatory
    Survival analysis
    Programmed cell death 1 receptor
    Phase-ii
    Pdcd1 protein, human
    Myeloid-derived suppressor cells
    Middle aged
    Male
    Lymphoma, large b-cell, diffuse
    Immunotherapy
    Immunomodulation
    Immunity
    Humans
    Gene expression regulation, neoplastic
    Female
    Clinical trials as topic
    Cellular
    Case-control studies
    Biomarkers, tumor
    Biomarkers
    Antineoplastic combined chemotherapy protocols
    Aged, 80 and over
    Aged
    Adult
    tumor
    rituximab
    myeloid-derived suppressor cells
    multicenter
    lenalidomide
    immunotherapy
    immunomodulation
    immunity
    gemcitabine
    expansion
    combination
    cellular
    breast-cancer
    blood
    association
    Pharmacology
    Oncology
    Molecular medicine
    Medicina i
    Immunology and allergy
    Immunology
    Cancer research
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