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多发性骨髓瘤诊断时及来那度胺维持治疗下的深度免疫特征分析

英文原题:Deep Immune Profiling of Multiple Myeloma at Diagnosis and under Lenalidomide Maintenance Therapy.

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Deep Immune Profiling of Multiple Myeloma at Diagnosis and under Lenalidomide Maintenance Therapy.

PubMed 2023/05/04(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

骨髓微环境与恶性细胞相互作用,并调控多发性骨髓瘤(MM)中的肿瘤存活和免疫逃逸。我们使用飞行时间流式细胞术研究了新诊断MM患者(n = 18)纵向骨髓样本的免疫特征。比较了对来那度胺/硼替佐米/地塞米松为基础的治疗反应良好(GR,n = 11)和反应不佳(BR,n = 7)的患者在治疗前和治疗期间的結果。治疗前,GR组的肿瘤细胞负荷较低,T细胞数量较高,其表型向表达细胞毒性相关标志物(CD45RA和CD57)的CD8+ T细胞偏移,CD8+终末效应细胞丰度较高,CD8+初始T细胞丰度较低。在自然杀伤(NK)细胞上,GR组基线时CD56(NCAM)、CD57和CD16表达增加,表明其成熟度和细胞毒性潜力。在以来那度胺为基础的治疗期间,GR患者显示效应记忆CD4+和CD8+ T细胞亚群增加。这些发现支持不同临床背景下存在不同的免疫模式,表明深度免疫分析可用于治疗指导,值得进一步探索。

展开英文摘要原文

The bone marrow microenvironment interacts with malignant cells and regulates cancer survival and immune evasion in multiple myeloma (MM).

We investigated the immune profiles of longitudinal bone marrow samples from patients with newly diagnosed MM ( n = 18) using cytometry by time-of-flight. The results before and during treatment were compared between patients with good (GR, n = 11) and bad (BR, n = 7) responses to lenalidomide/bortezomib/dexamethasone-based treatment.

Before treatment, the GR group had a lower tumor cell burden and a higher number of T cells with a phenotype shifted toward CD8+ T cells expressing markers attributed to cytotoxicity (CD45RA and CD57), a higher abundance of CD8+ terminal effector cells, and a lower abundance of CD8+ naïve T cells.

On natural killer (NK) cells, increased expression of CD56 (NCAM), CD57, and CD16 was seen at baseline in the GR group, indicating their maturation and cytotoxic potential. During lenalidomide-based treatment, the GR patients showed an increase in effector memory CD4+ and CD8+ T-cell subsets.

These findings support distinct immune patterns in different clinical contexts, suggesting that deep immune profiling could be used for treatment guidance and warrants further exploration.

论文信息

作者
Luoma S、Sergeev P、Javarappa KK、Öhman TJ、Varjosalo M、Säily M、Anttila P、Sankelo M
单位
Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, 00290 Helsinki, Finland.Finland
期刊
Cancers2023 May 4
原文标识
PubMed 37174069 · DOI 10.3390/cancers15092604