在复发/难治性弥漫性大B细胞淋巴瘤的R2-GDP-GOTEL试验中，CD8+自然杀伤细胞作为来那度胺联合R-GDP实现完全缓解和生存的潜在生物标志物。
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.
作者信息
Hontecillas-Prieto Lourdes, García-Domínguez Daniel J, Palazón-Carrión Natalia, Martín García-Sancho Alejandro, Nogales-Fernández Esteban, Jiménez-Cortegana Carlos, Sánchez-León María L, Silva-Romeiro Silvia, Flores-Campos Rocío, Carnicero-González Fernando, Ríos-Herranz Eduardo, de la Cruz-Vicente Fátima, Rodríguez-García Guillermo, Fernández-Álvarez Rubén, Martínez-Banaclocha Natividad, Gumà-Padrò Josep, Gómez-Codina José, Salar-Silvestre Antonio, Rodríguez-Abreu Delvys, Gálvez-Carvajal Laura, Labrador Jorge, Guirado-Risueño María, Provencio-Pulla Mariano, Sánchez-Beato Margarita, Marylene Lejeune, Álvaro-Naranjo Tomás, Casanova-Espinosa María, Rueda-Domínguez Antonio, Sánchez-Margalet Víctor, de la Cruz-Merino Luis
机构信息
Clinical Biochemistry Service, Virgen Macarena University Hospital, University of Seville, Seville, Spain.
Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, Spain.
出版信息
Front Immunol. 2024 Feb 26;15:1293931. doi: 10.3389/fimmu.2024.1293931. eCollection 2024.
BACKGROUND
Diffuse 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.
METHODS
78 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.
RESULTS
Our 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.
CONCLUSION
CD8+ 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 REGISTRATION
https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.
背景
弥漫性大B细胞淋巴瘤（DLBCL）是全球最常见的非霍奇金淋巴瘤。DLBCL是一种侵袭性疾病，可通过前期标准化疗免疫治疗方案治愈。然而，约35%-40%的DLBCL患者会复发，因此，特别是在这种情况下，寻找新的预后和预测生物标志物迫在眉睫。自然杀伤（NK）细胞是效应细胞，因其细胞毒性能力在抗肿瘤免疫中发挥重要作用，而循环中表达CD8的NK细胞亚群具有更高的细胞毒性功能。在这项R2-GDP-GOTEL试验的子研究中，我们评估了血液中CD8+NK细胞作为复发/难治性（R/R）DLBCL患者治疗反应和生存的预测指标。
方法
78例患者在II期试验中接受了R2-GDP方案。通过流式细胞术分析血样。进行统计分析以确定R/R DLBCL患者基线时CD8+NK细胞的预后潜力。
结果
我们的结果显示，R/R DLBCL患者循环中CD8+NK细胞的数量低于健康供体，且在治疗期间和治疗后没有变化。然而，基线时血液中CD8+NK细胞水平与R/R DLBCL患者的完全缓解相关。此外，我们还证明，CD8+NK细胞水平在R/R DLBCL患者的总生存方面具有潜在的预后价值。
结论
CD8+NK细胞代表一种具有预测和预后潜力的新生物标志物，在R/R DLBCL患者的临床管理中应予以考虑。
临床试验注册
https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 欧洲临床试验注册中心，编号：2014-001620-29。
Zotero 插件