文章：

免疫调节性恶性B细胞促进慢性淋巴细胞白血病进展

Immuno-regulatory malignant B cells contribute to Chronic Lymphocytic Leukemia progression 

原文发布日期：2023-03-28 

英文摘要：

Chronic Lymphocytic Leukemia (CLL) is a heterogeneous B cell neoplasm ranging from indolent to rapidly progressive disease. Leukemic cell subsets with regulatory properties evade immune clearance; however, the contribution of such subsets during CLL progression is not completely elucidated. Here, we report that CLL B cells crosstalk with their immune counterparts, notably by promoting the regulatory T (Treg) cell compartment and shaping several helper T (Th) subsets. Among various constitutively- and BCR/CD40-mediated factors secreted, tumour subsets co-express two important immunoregulatory cytokines, IL10 and TGFβ1, both associated with a memory B cell phenotype. Neutralizing secreted IL10 or inhibiting the TGFβ signalling pathway demonstrated that these cytokines are mainly involved in Th- and Treg differentiation/maintenance. In line with the regulatory subsets, we also demonstrated that a CLL B cell population expresses FOXP3, a marker of regulatory T cells. Analysis of IL10, TGFβ1 and FOXP3 positive subpopulations frequencies in CLL samples discriminated 2 clusters of untreated CLL patients that were significantly different in Tregs frequency and time-to-treatment. Since this distinction was pertinent to disease progression, the regulatory profiling provides a new rationale for patient stratification and sheds light on immune dysfunction in CLL. 

摘要翻译： 

慢性淋巴细胞白血病（CLL）是一种异质性B细胞肿瘤，其病程可从惰性发展至快速进展。具有调节特性的白血病细胞亚群通过逃避免疫清除而存活，然而这类亚群在CLL进展中的具体作用尚未完全阐明。本研究发现CLL B细胞与其免疫对应细胞存在交互作用，特别是通过促进调节性T细胞（Treg）区室形成并塑造多种辅助性T细胞（Th）亚群。在组成性及BCR/CD40通路介导分泌的多种因子中，肿瘤亚群共表达两种重要免疫调节细胞因子——IL10和TGFβ1，二者均与记忆性B细胞表型相关。通过中和分泌的IL10或抑制TGFβ信号通路证实，这些细胞因子主要参与Th和Treg细胞的分化/维持。与调节亚群相一致，我们还证实存在表达Treg细胞标志物FOXP3的CLL B细胞群体。对CLL样本中IL10、TGFβ1和FOXP3阳性亚群频率的分析，可将未治疗CLL患者区分为两个集群，其在Treg频率和至治疗时间方面存在显著差异。由于这种区分与疾病进展密切相关，调节特征谱为患者分层提供了新的理论依据，并揭示了CLL中的免疫功能障碍机制。

原文链接：

Immuno-regulatory malignant B cells contribute to Chronic Lymphocytic Leukemia progression