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.

Autor:	Jiménez-Cortegana C; Medical Biochemistry and Molecular Biology and Immunology, Virgen Macarena University Hospital, Sevilla, Seville, Spain., Palazón-Carrión N, Martin Garcia-Sancho A; Hematology Dept, Hospital Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain., Nogales-Fernandez E; Clinical Oncology Dept. Medicine Department, University of Seville, Virgen Macarena University Hospital, Seville, Spain., Carnicero-González F; Hematology Dept, San Pedro de Alcántara Hospital, Cáceres, Spain., Ríos-Herranz E; Hematology Dept, Virgen de Valme University Hospital, Seville, Spain., de la Cruz-Vicente F; Hematology Dept, Virgen del Rocío University Hospital, Seville, Spain., Rodríguez-García G; Hematology Dept, Virgen del Rocío University Hospital, Seville, Spain., Fernández-Álvarez R; Hematology Dept, Cabueñes Hospital, Gijón, Spain., Rueda Dominguez A; Hematology/ClinicalOncology Dept, Costa del Sol Hospital, Marbella, Málaga, Spain., Casanova-Espinosa M; Hematology/ClinicalOncology Dept, Costa del Sol Hospital, Marbella, Málaga, Spain., Martínez-Banaclocha N; Clinical Oncology Dept, Alicante General University Hospital, Alicante, Spain., Gumà-Padrò J; Clinical Oncology Dept, Sant Joan de Reus University Hospital URV, IISPV, Reus, Spain., Gómez-Codina J; Clinical Oncology Dept, La Fé University Hospital, Valencia, Spain., Labrador J; Hematology Dept, Hospital Universitario de Burgos, Burgos, Spain., Salar-Silvestre A; Hematology Dept, Hospital del Mar, Barcelona, Spain., Rodriguez-Abreu D; Clinical Oncology Dept, Insular University Hospital, Las Palmas de Gran Canaria, Spain., Galvez-Carvajal L; Unidad de Gestión Clínica Intercentros de Oncología Médica de Málaga, Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain., Provencio M; Clinical Oncology Dept, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain., Sánchez-Beato M; Lymphoma Research Group, Clinical Oncology Dept, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid, Spain., Guirado-Risueño M; Clinical Oncology Dept, Elche General University Hospital General, Elche, Alicante, Spain., Espejo-García P; Clinical Oncology Dept. Medicine Department, University of Seville, Virgen Macarena University Hospital, Seville, Spain., Lejeune M; Pathology Department, Plataforma de Estudios Histológicos, Citológicos y de Digitalización, Hospital de Tortosa Verge de la Cinta, IISPV, URV, Tortosa, Tarragona, Spain., Álvaro T; Pathology Dept, Hospital de Tortosa Verge de la Cinta, Catalan Institute of Health, Institut d'Investigació Sanitària Pere Virgili (IISPV), Tortosa, Tarragona, Spain., Sánchez-Margalet V; Medical Biochemistry and Molecular Biology and Immunology, Virgen Macarena University Hospital, Sevilla, Seville, Spain margalet@us.es ldelacruzmerino@gmail.com., de la Cruz-Merino L
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2021 Jun; Vol. 9 (6).
DOI:	10.1136/jitc-2020-002323
Abstrakt:	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. Competing Interests: Competing interests: None declared. (© 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.)
Databáze:	MEDLINE
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