Luoma Sini, Sergeev Philipp, Javarappa Komal Kumar, Öhman Tiina J, Varjosalo Markku, Säily Marjaana, Anttila Pekka, Sankelo Marja, Partanen Anu, Nihtinen Anne, Heckman Caroline A, Silvennoinen Raija
Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, 00290 Helsinki, Finland.
Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00290 Helsinki, Finland.
Cancers (Basel). 2023 May 4;15(9):2604. doi: 10.3390/cancers15092604.
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 ( = 18) using cytometry by time-of-flight. The results before and during treatment were compared between patients with good (GR, = 11) and bad (BR, = 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.
骨髓微环境与恶性细胞相互作用，并调节多发性骨髓瘤（MM）中的癌症存活和免疫逃逸。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谱。比较了来那度胺/硼替佐米/地塞米松治疗反应良好（GR，n = 11）和反应不良（BR，n = 7）患者治疗前和治疗期间的结果。治疗前，GR组的肿瘤细胞负荷较低，具有向表达细胞毒性相关标志物（CD45RA和CD57）的CD8 + T细胞偏移表型的T细胞数量较多，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的表达增加，表明它们的成熟和细胞毒性潜力。在基于来那度胺的治疗期间，GR患者的效应记忆CD4 + 和CD8 + T细胞亚群增加。这些发现支持不同临床背景下的独特免疫模式，表明深度免疫谱分析可用于治疗指导，值得进一步探索。
