Department of Immunology, Faculty of Medicine and Dentistry, Palacký University and University Hospital Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic.
Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology NAS RA, Yerevan, Armenia.
Sci Rep. 2021 Jan 11;11(1):322. doi: 10.1038/s41598-020-79121-4.
The tissue microenvironment in chronic lymphocytic leukaemia (CLL) plays a key role in the pathogenesis of CLL, but the complex blood microenvironment in CLL has not yet been fully characterised. Therefore, immunophenotyping of circulating immune cells in 244 CLL patients and 52 healthy controls was performed using flow cytometry and analysed by multivariate Patient Similarity Networks (PSNs). Our study revealed high inter-individual heterogeneity in the distribution and activation of bystander immune cells in CLL, depending on the bulk of the CLL cells. High CLL counts were associated with low activation on circulating monocytes and T cells and vice versa. The highest activation of immune cells, particularly of intermediate and non-classical monocytes, was evident in patients treated with novel agents. PSNs revealed a low activation of immune cells in CLL progression, irrespective of IgHV status, Binet stage and TP53 disruption. Patients with high intermediate monocytes (> 5.4%) with low activation were 2.5 times more likely (95% confidence interval 1.421-4.403, P = 0.002) to had shorter time-to-treatment than those with low monocyte counts. Our study demonstrated the association between the activation of circulating immune cells and the bulk of CLL cells. The highest activation of bystander immune cells was detected in patients with slow disease course and in those treated with novel agents. The subset of intermediate monocytes showed predictive value for time-to-treatment in CLL.
慢性淋巴细胞白血病（CLL）中的组织微环境在 CLL 的发病机制中起着关键作用，但 CLL 中复杂的血液微环境尚未得到充分描述。因此，我们使用流式细胞术对 244 例 CLL 患者和 52 名健康对照者的循环免疫细胞进行了免疫表型分析，并通过多变量患者相似网络（PSN）进行了分析。我们的研究表明，在 CLL 中，旁观者免疫细胞的分布和激活存在高度的个体间异质性，这取决于 CLL 细胞的总量。CLL 计数较高与循环单核细胞和 T 细胞的低激活相关，反之亦然。在接受新型药物治疗的患者中，免疫细胞的激活程度最高，尤其是中间型和非经典型单核细胞。PSN 显示，无论 IgHV 状态、Binet 分期和 TP53 缺失如何，CLL 进展过程中免疫细胞的激活程度都较低。与低活化中间单核细胞（>5.4%）患者相比，高活化中间单核细胞（>5.4%）患者的治疗时间更短，其可能性是后者的 2.5 倍（95%置信区间为 1.421-4.403，P=0.002）。我们的研究表明，循环免疫细胞的激活与 CLL 细胞的总量之间存在关联。在疾病进程缓慢的患者和接受新型药物治疗的患者中，旁观者免疫细胞的激活程度最高。中间型单核细胞亚群对 CLL 的治疗时间具有预测价值。
