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多发性骨髓瘤患者外周血中的淋巴细胞谱

Lymphocyte profile in peripheral blood of patients with multiple myeloma.

作者信息

Dekojová Tereza, Gmucová Hana, Macečková Diana, Klieber Robin, Ostašov Pavel, Leba Martin, Vlas Tomáš, Jungová Alexandra, Caputo Valentina S, Čedíková Miroslava, Lysák Daniel, Jindra Pavel, Holubová Monika

机构信息

Department of Haematology and Oncology, University Hospital Pilsen, Pilsen, 323 00, Czech Republic.

Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Pilsen, 323 00, Czech Republic.

出版信息

Ann Hematol. 2024 Dec;103(12):5615-5625. doi: 10.1007/s00277-024-05820-x. Epub 2024 Jun 4.

Abstract

Multiple myeloma (MM) is a disease which remains incurable. One of the main reasons is a weakened immune system that allows MM cells to survive. Therefore, the current research is focused on the study of immune system imbalance in MM to find the most effective immunotherapy strategies. Aiming to identify the key points of immune failure in MM patients, we analysed peripheral lymphocytes subsets from MM patients (n = 57) at various stages of the disease course and healthy individuals (HI, n = 15) focusing on T, NK, iNKT, B cells and NK-cell cytokines. Our analysis revealed that MM patients exhibited immune alterations in all studied immune subsets. Compared to HI, MM patients had a significantly lower proportion of CD4 + T cells (19.55% vs. 40.85%; p < 0.001) and CD4 + iNKT cells (18.8% vs. 40%; p < 0.001), within B cells an increased proportion of CD21LCD38L subset (4.5% vs. 0.4%; p < 0.01) and decreased level of memory cells (unswitched 6.1% vs. 14.7%; p < 0.001 and switched 7.8% vs. 11.2%; NS), NK cells displaying signs of activation and exhaustion characterised by a more than 2-fold increase in SLAMF7 MFI (p < 0.001), decreased expression of NKG2D (MFI) and NKp46 (%) on CD16 + 56 + and CD16 + 56- subset respectively (p < 0.05), Effective immunotherapy needs to consider these immune defects and monitoring of the immune status of MM patients is essential to define better interventions in the future.

摘要

多发性骨髓瘤(MM)是一种仍无法治愈的疾病。主要原因之一是免疫系统减弱,使得MM细胞得以存活。因此,当前的研究聚焦于MM中免疫系统失衡的研究,以找到最有效的免疫治疗策略。为了确定MM患者免疫失败的关键点,我们分析了处于疾病进程不同阶段的MM患者(n = 57)和健康个体(HI,n = 15)的外周淋巴细胞亚群,重点关注T细胞、NK细胞、iNKT细胞、B细胞和NK细胞细胞因子。我们的分析表明,MM患者在所有研究的免疫亚群中均表现出免疫改变。与HI相比,MM患者的CD4 + T细胞比例显著降低(19.55% 对 40.85%;p < 0.001)和CD4 + iNKT细胞比例显著降低(18.8% 对 40%;p < 0.001),在B细胞中,CD21LCD38L亚群比例增加(4.5% 对 0.4%;p < 0.01)且记忆细胞水平降低(未转换的6.1% 对 14.7%;p < 0.001,转换的7.8% 对 11.2%;无显著性差异),NK细胞表现出激活和耗竭的迹象,其特征是SLAMF7平均荧光强度(MFI)增加超过2倍(p < 0.001),CD16 + 56 + 和CD16 + 56 - 亚群上NKG2D(MFI)和NKp46(%)的表达分别降低(p < 0.05),有效的免疫治疗需要考虑这些免疫缺陷,并且监测MM患者的免疫状态对于确定未来更好的干预措施至关重要。

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